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15 pages, 2396 KiB

Open AccessArticle

Structural Analysis of the Large Stokes Shift Red Fluorescent Protein tKeima

by Ki Hyun Nam and Yongbin Xu

Molecules 2024, 29(11), 2579; https://doi.org/10.3390/molecules29112579 - 30 May 2024

Viewed by 317

Abstract

The Keima family comprises large Stokes shift fluorescent proteins that are useful for dual-color fluorescence cross-correlation spectroscopy and multicolor imaging. The tKeima is a tetrameric large Stokes shift fluorescent protein and serves as the ancestor fluorescent protein for both dKeima and mKeima. The [...] Read more.

The Keima family comprises large Stokes shift fluorescent proteins that are useful for dual-color fluorescence cross-correlation spectroscopy and multicolor imaging. The tKeima is a tetrameric large Stokes shift fluorescent protein and serves as the ancestor fluorescent protein for both dKeima and mKeima. The spectroscopic properties of tKeima have been previously reported; however, its structural basis and molecular properties have not yet been elucidated. In this study, we present the crystallographic results of the large Stokes shift fluorescent protein tKeima. The purified tKeima protein spontaneously crystallized after purification without further crystallization. The crystal structure of tKeima was determined at 3.0 Å resolution, revealing a β-barrel fold containing the Gln-Tyr-Gly chromophores mainly with cis-conformation. The tetrameric interfaces of tKeima were stabilized by numerous hydrogen bonds and salt–bridge interactions. These key residues distinguish the substituted residues in dKeima and mKeima. The key structure-based residues involved in the tetramer formation of tKeima provide insights into the generation of a new type of monomeric mKeima. This structural analysis expands our knowledge of the Keima family and provides insights into its protein engineering. Full article

(This article belongs to the Special Issue Protein Structure, Function and Interaction)

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12 pages, 1409 KiB

Open AccessArticle

Study of pH and Thermodynamic Parameters via Circular Dichroism Spectroscopy of a Recombinant Human Lactoferrin

by Beatriz L. Álvarez-Mayorga, Sergio Romero-Gómez, Jorge L. Rosado, Janet Ocampo-Hernández, J. Gómez-Guzmán and Luis Ortiz-Frade

Molecules 2024, 29(2), 491; https://doi.org/10.3390/molecules29020491 - 19 Jan 2024

Viewed by 1042

Abstract

The production of human recombinant proteins to be used for therapeutic or nutritional purposes must focus on obtaining a molecule that is as close as possible to the native human protein. This biotechnological tool has been documented in various studies published in recent [...] Read more.

The production of human recombinant proteins to be used for therapeutic or nutritional purposes must focus on obtaining a molecule that is as close as possible to the native human protein. This biotechnological tool has been documented in various studies published in recent decades, with lactoferrin being one of those that has generated the most interest, being a promising option for recombinant technology. However, stability studies including thermodynamic parameters have not been reported for recombinant lactoferrin (Lf). The objective of this work was to obtain the human recombinant protein using the yeast Komagataella phaffii to study structural changes modifying pH and temperature using circular dichroism spectroscopy (CD). Thermodynamic parameters such as ΔH, ΔS and Tm were calculated and compared with commercial human lactoferrin. We propose the potential use of CD and thermodynamic parameters as a criterion in the production of recombinant proteins to be used in the production of specialized recombinant proteins. Full article

(This article belongs to the Special Issue Protein Structure, Function and Interaction)

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14 pages, 2094 KiB

Open AccessArticle

Enhanced Activity and Stability of an Acetyl Xylan Esterase in Hydrophilic Alcohols through Site-Directed Mutagenesis

by Henry Madubuike and Natalie Ferry

Molecules 2023, 28(21), 7393; https://doi.org/10.3390/molecules28217393 - 2 Nov 2023

Cited by 1 | Viewed by 1031

Abstract

Current demands for the development of suitable biocatalysts showing high process performance is stimulated by the need to replace current chemical synthesis with cleaner alternatives. A drawback to the use of biocatalysts for unique applications is their low performance in industrial conditions. Hence, [...] Read more.

Current demands for the development of suitable biocatalysts showing high process performance is stimulated by the need to replace current chemical synthesis with cleaner alternatives. A drawback to the use of biocatalysts for unique applications is their low performance in industrial conditions. Hence, enzymes with improved performance are needed to achieve innovative and sustainable biocatalysis. In this study, we report the improved performance of an engineered acetyl xylan esterase (BaAXE) in a hydrophilic organic solvent. The structure of BaAXE was partitioned into a substrate-binding region and a solvent-affecting region. Using a rational design approach, charged residues were introduced at protein surfaces in the solvent-affecting region. Two sites present in the solvent-affecting region, A12D and Q143E, were selected for site-directed mutagenesis, which generated the mutants MUT12, MUT143 and MUT12-143. The mutants MUT12 and MUT143 reported lower Km (0.29 mM and 0.27 mM, respectively) compared to the wildtype (0.41 mM). The performance of the mutants in organic solvents was assessed after enzyme incubation in various strengths of alcohols. The mutants showed improved activity and stability compared to the wild type in low strengths of ethanol and methanol. However, the activity of MUT143 was lost in 40% methanol while MUT12 and MUT12-143 retained over 70% residual activity in this environment. Computational analysis links the improved performance of MUT12 and MUT12-143 to novel intermolecular interactions that are absent in MUT143. This work supports the rationale for protein engineering to augment the characteristics of wild-type proteins and provides more insight into the role of charged residues in conferring stability. Full article

(This article belongs to the Special Issue Protein Structure, Function and Interaction)

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13 pages, 4324 KiB

Open AccessArticle

Glycosylation Contributes to Thermostability and Proteolytic Resistance of rFIP-nha (Nectria haematococca)

by Yusi Liu, Tamara Hoppenbrouwers, Yulu Wang, Yingying **e, Xue Wei, Haowen Zhang, Guoming Du, Khandader Md Sharif Uddin Imam, Harry Wichers, Zhen Li and Shanna Bastiaan-Net

Molecules 2023, 28(17), 6386; https://doi.org/10.3390/molecules28176386 - 31 Aug 2023

Cited by 1 | Viewed by 1091

Abstract

Glycosylation is an important post-translational modification of proteins, contributing to protein function, stability and subcellular localization. Fungal immunomodulatory proteins (FIPs) are a group of small proteins with notable immunomodulatory activity, some of which are glycoproteins. In this study, the impact of glycosylation on [...] Read more.

Glycosylation is an important post-translational modification of proteins, contributing to protein function, stability and subcellular localization. Fungal immunomodulatory proteins (FIPs) are a group of small proteins with notable immunomodulatory activity, some of which are glycoproteins. In this study, the impact of glycosylation on the bioactivity and biochemical characteristics of FIP-nha (from Nectria haematococca) is described. Three rFIP-nha glycan mutants (N5A, N39A, N5+39A) were constructed and expressed in Pichia pastoris to study the functionality of the specific N-glycosylation on amino acid N5 and N39. Their protein characteristics, structure, stability and activity were tested. WT and mutants all formed tetramers, with no obvious difference in crystal structures. Their melting temperatures were 82.2 °C (WT), 81.4 °C (N5A), 80.7 °C (N39A) and 80.1 °C (N5+39A), indicating that glycosylation improves thermostability of rFIP-nha. Digestion assays showed that glycosylation on either site improved pepsin resistance, while 39N-glycosylation was important for trypsin resistance. Based on the 3D structure and analysis of enzyme cleavage sites, we conclude that glycosylation might interfere with hydrolysis via increasing steric hindrance. WT and mutants exerted similar bioactivity on tumor cell metabolism and red blood cells hemagglutination. Taken together, these findings indicate that glycosylation of FIP-nha impacts its thermostability and digestion resistance. Full article

(This article belongs to the Special Issue Protein Structure, Function and Interaction)

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20 pages, 5589 KiB

Open AccessArticle

An Integrated Computational Analysis of High-Risk SNPs in Angiopoietin-like Proteins (ANGPTL3 and ANGPTL8) Reveals Perturbed Protein Dynamics Associated with Cancer

by Sajid Iqbal, Farida Begum, Dorothy Wavinya Nyamai, Nasir Jalal and Peter Shaw

Molecules 2023, 28(12), 4648; https://doi.org/10.3390/molecules28124648 - 8 Jun 2023

Cited by 1 | Viewed by 1553

Abstract

Angiopoietin-like proteins (ANGPTL) constitute a family of eight proteins (1–8) which play a pivotal role in the regulation of various pathophysiological processes. The current study sought to identify high-risk, “non-synonymous, single-nucleotide polymorphisms” (nsSNPs) in both ANGPTL3 and ANGPTL8 to evaluate the role that [...] Read more.

Angiopoietin-like proteins (ANGPTL) constitute a family of eight proteins (1–8) which play a pivotal role in the regulation of various pathophysiological processes. The current study sought to identify high-risk, “non-synonymous, single-nucleotide polymorphisms” (nsSNPs) in both ANGPTL3 and ANGPTL8 to evaluate the role that these nsSNPs play in various types of cancer. We retrieved a total of 301 nsSNPs from various databases; 79 of these candidates constitute high-risk nsSNPs. Moreover, we identified eleven high-risk nsSNPs that cause various types of cancer: seven candidates for ANGPTL3 (L57H, F295L, L309F, K329M, R332L, S348C, and G409R) and four candidates for ANGPTL8 (P23L, R85W, R138S, and E148D). Protein–protein interaction analysis revealed a strong association of ANGPTL proteins with several tumor-suppressor proteins such as ITGB3, ITGAV, and RASSF5. ‘Gene-expression profiling interactive analysis’ (GEPIA) showed that expression of ANGPTL3 is significantly downregulated in five cancers: sarcoma (SARC); cholangio carcinoma (CHOL); kidney chromophobe carcinoma (KICH); kidney renal clear cell carcinoma (KIRC); and kidney renal papillary cell carcinoma (KIRP). GEPIA also showed that expression of ANGPTL8 remains downregulated in three cancers: CHOL; glioblastoma (GBM); and breast invasive carcinoma (BRCA). Survival rate analysis indicated that both upregulation and downregulation of ANGPTL3 and ANGPTL8 leads to low survival rates in various types of cancer. Overall, the current study revealed that both ANGPTL3 and ANGPTL8 constitute potential prognostic biomarkers for cancer; moreover, nsSNPs in these proteins might lead to the progression of cancer. However, further in vivo investigation will be helpful to validate the role of these proteins in the biology of cancer. Full article

(This article belongs to the Special Issue Protein Structure, Function and Interaction)

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11 pages, 2703 KiB

Open AccessArticle

Structural Analysis of Spermidine Synthase from Kluyveromyces lactis

by Seong** Kim and Jeong Ho Chang

Molecules 2023, 28(8), 3446; https://doi.org/10.3390/molecules28083446 - 13 Apr 2023

Viewed by 1387

Abstract

Spermidine is a polyamine molecule that performs various cellular functions, such as DNA and RNA stabilization, autophagy modulation, and eIF5A formation, and is generated from putrescine by aminopropyltransferase spermidine synthase (SpdS). During synthesis, the aminopropyl moiety is donated from decarboxylated S-adenosylmethionine to form [...] Read more.

Spermidine is a polyamine molecule that performs various cellular functions, such as DNA and RNA stabilization, autophagy modulation, and eIF5A formation, and is generated from putrescine by aminopropyltransferase spermidine synthase (SpdS). During synthesis, the aminopropyl moiety is donated from decarboxylated S-adenosylmethionine to form putrescine, with 5′-deoxy-5′-methylthioadenosine being produced as a byproduct. Although the molecular mechanism of SpdS function has been well-established, its structure-based evolutionary relationships remain to be fully understood. Moreover, only a few structural studies have been conducted on SpdS from fungal species. Here, we determined the crystal structure of an apo-form of SpdS from Kluyveromyces lactis (KlSpdS) at 1.9 Å resolution. Structural comparison with its homologs revealed a conformational change in the α6 helix linked to the gate-kee** loop, with approximately 40° outward rotation. This change caused the catalytic residue Asp170 to move outward, possibly due to the absence of a ligand in the active site. These findings improve our understanding of the structural diversity of SpdS and provide a missing link that expands our knowledge of the structural features of SpdS in fungal species. Full article

(This article belongs to the Special Issue Protein Structure, Function and Interaction)

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15 pages, 4966 KiB

Open AccessArticle

Evolutionary Couplings and Molecular Dynamic Simulations Highlight Details of GPCRs Heterodimers’ Interfaces

by Karim Widad Temgbet Nchourupouo, Jules Nde, Yannick Joel Wadop Ngouongo, Serge Sylvain Zekeng and Bernard Fongang

Molecules 2023, 28(4), 1838; https://doi.org/10.3390/molecules28041838 - 15 Feb 2023

Cited by 2 | Viewed by 1784

Abstract

A growing body of evidence suggests that only a few amino acids (“hot-spots”) at the interface contribute most of the binding energy in transient protein-protein interactions. However, experimental protocols to identify these hot-spots are highly labor-intensive and expensive. Computational methods, including evolutionary couplings, [...] Read more.

A growing body of evidence suggests that only a few amino acids (“hot-spots”) at the interface contribute most of the binding energy in transient protein-protein interactions. However, experimental protocols to identify these hot-spots are highly labor-intensive and expensive. Computational methods, including evolutionary couplings, have been proposed to predict the hot-spots, but they generally fail to provide details of the interacting amino acids. Here we showed that unbiased evolutionary methods followed by biased molecular dynamic simulations could achieve this goal and reveal critical elements of protein complexes. We applied the methodology to selected G-protein coupled receptors (GPCRs), known for their therapeutic properties. We used the structure-prior-assisted direct coupling analysis (SP-DCA) to predict the binding interfaces of A2aR/D2R, CB1R/D2R, A2aR/CB1R, 5HT2AR/D2R, and 5-HT2AR/mGluR2 receptor heterodimers, which all agreed with published data. In order to highlight details of the interactions, we performed molecular dynamic (MD) simulations using the newly developed AWSEM energy model. We found that these receptors interact primarily through critical residues at the C and N terminal domains and the third intracellular loop (ICL3). The MD simulations showed that these residues are energetically necessary for dimerization and revealed their native conformational state. We subsequently applied the methodology to the 5-HT2AR/5-HTR4R heterodimer, given its implication in drug addiction and neurodegenerative pathologies such as Alzheimer’s disease (AD). Further, the SP-DCA analysis showed that 5-HT2AR and 5-HTR4R heterodimerize through the C-terminal domain of 5-HT2AR and ICL3 of 5-HT4R. However, elucidating the details of GPCR interactions would accelerate the discovery of druggable sites and improve our knowledge of the etiology of common diseases, including AD. Full article

(This article belongs to the Special Issue Protein Structure, Function and Interaction)

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18 pages, 6066 KiB

Open AccessArticle

The Structural Basis of African Swine Fever Virus pS273R Protease Binding to E64 through Molecular Dynamics Simulations

by Gen Lu, Kang Ou, Yiwen **g, Huan Zhang, Shouhua Feng, Zuofeng Yang, Guoshun Shen, **ling Liu, Changde Wu and Shu Wei

Molecules 2023, 28(3), 1435; https://doi.org/10.3390/molecules28031435 - 2 Feb 2023

Cited by 1 | Viewed by 1739

Abstract

Identification of novel drugs for anti-African swine fever (ASF) applications is of utmost urgency, as it negatively affects pig farming and no effective vaccine or treatment is currently available. African swine fever virus (ASFV) encoded pS273R is a cysteine protease that plays an [...] Read more.

Identification of novel drugs for anti-African swine fever (ASF) applications is of utmost urgency, as it negatively affects pig farming and no effective vaccine or treatment is currently available. African swine fever virus (ASFV) encoded pS273R is a cysteine protease that plays an important role in virus replication. E64, acting as an inhibitor of cysteine protease, has been established as exerting an inhibitory effect on pS273R. In order to obtain a better understanding of the interaction between E64 and pS273R, common docking, restriction docking, and covalent docking were employed to analyze the optimal bonding position between pS273R−E64 and its bonding strength. Additionally, three sets of 100 ns molecular dynamics simulations were conducted to examine the conformational dynamics of pS273R and the dynamic interaction of pS273R−E64, based on a variety of analytical methods including root mean square deviation (RMSD), root mean square fluctuation (RMSF), free energy of ligand (FEL), principal component analysis (PCA), and molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) analysis. The results show that E64 and pS273R exhibited close binding degrees at the activity center of ASFV pS273R protease. The data of these simulations indicate that binding of E64 to pS273R results in a reduction in flexibility, particularly in the ARM region, and a change in the conformational space of pS273R. Additionally, the ability of E64 to interact with polar amino acids such as ASN158, SER192, and GLN229, as well as charged amino acids such as LYS167 and HIS168, seems to be an important factor in its inhibitory effect. Finally, Octet biostratigraphy confirmed the binding of E64 and pS273R with a KD value of 903 uM. Overall, these findings could potentially be utilized in the development of novel inhibitors of pS273R to address the challenges posed by ASFV. Full article

(This article belongs to the Special Issue Protein Structure, Function and Interaction)

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9 pages, 1463 KiB

Open AccessArticle

The Mitochondrial Protein MitoNEET as a Probe for the Allostery of Glutamate Dehydrogenase

by Chimere Nnatubeugo, Erica Johnson, Sarah Gisondi, Felicia Roland, Werner J. Geldenhuys, Michael A. Menze and Mary E. Konkle

Molecules 2022, 27(23), 8314; https://doi.org/10.3390/molecules27238314 - 29 Nov 2022

Cited by 1 | Viewed by 1680

Abstract

The proteins glutamate dehydrogenase (GDH) and mitoNEET are both targets of drug development efforts to treat metabolic disorders, cancer, and neurodegenerative diseases. However, these two proteins differ starkly in the current knowledge about ligand binding sites. MitoNEET is a [2Fe-2S]-containing protein with no [...] Read more.

The proteins glutamate dehydrogenase (GDH) and mitoNEET are both targets of drug development efforts to treat metabolic disorders, cancer, and neurodegenerative diseases. However, these two proteins differ starkly in the current knowledge about ligand binding sites. MitoNEET is a [2Fe-2S]-containing protein with no obvious binding site for small ligands observed in its crystal structures. In contrast, GDH is known to have a variety of ligands at multiple allosteric sites thereby leading to complex regulation in activity. In fact, while GDH can utilize either NAD(H) or NADP(H) for catalysis at the active site, only NAD(H) binds at a regulatory site to inhibit GDH activity. Previously, we found that mitoNEET forms a covalent bond with GDH in vitro and increases the catalytic activity of the enzyme. In this study we evaluated the effects of mitoNEET binding on the allosteric control of GDH conferred by inhibitors. We examined all effectors using NAD or NADP as the coenzyme to determine allosteric linkage by the NAD-binding regulatory site. We found that GDH activity, in the presence of the inhibitory palmitoyl-CoA and EGCG, can be rescued by mitoNEET, regardless of the coenzyme used. This suggests that mitoNEET rescues GDH by stabilizing the open conformation. Full article

(This article belongs to the Special Issue Protein Structure, Function and Interaction)

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14 pages, 3161 KiB

Open AccessArticle

Analysis of Protein-Protein Interactions for Intermolecular Bond Prediction

by Justin Z. Tam, Talulla Palumbo, Julie M. Miwa and Brian Y. Chen

Molecules 2022, 27(19), 6178; https://doi.org/10.3390/molecules27196178 - 21 Sep 2022

Cited by 4 | Viewed by 1884

Abstract

Protein-protein interactions often involve a complex system of intermolecular interactions between residues and atoms at the binding site. A comprehensive exploration of these interactions can help reveal key residues involved in protein-protein recognition that are not obvious using other protein analysis techniques. This [...] Read more.

Protein-protein interactions often involve a complex system of intermolecular interactions between residues and atoms at the binding site. A comprehensive exploration of these interactions can help reveal key residues involved in protein-protein recognition that are not obvious using other protein analysis techniques. This paper presents and extends DiffBond, a novel method for identifying and classifying intermolecular bonds while applying standard definitions of bonds in chemical literature to explain protein interactions. DiffBond predicted intermolecular bonds from four protein complexes: Barnase-Barstar, Rap1a-raf, SMAD2-SMAD4, and a subset of complexes formed from three-finger toxins and nAChRs. Based on validation through manual literature search and through comparison of two protein complexes from the SKEMPI dataset, DiffBond was able to identify intermolecular ionic bonds and hydrogen bonds with high precision and recall, and identify salt bridges with high precision. DiffBond predictions on bond existence were also strongly correlated with observations of Gibbs free energy change and electrostatic complementarity in mutational experiments. DiffBond can be a powerful tool for predicting and characterizing influential residues in protein-protein interactions, and its predictions can support research in mutational experiments and drug design. Full article

(This article belongs to the Special Issue Protein Structure, Function and Interaction)

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10 pages, 2308 KiB

Open AccessArticle

Structural and Functional Analysis of the Pyridoxal Phosphate Homeostasis Protein YggS from Fusobacterium nucleatum

by Shanru He, Yuanyuan Chen, Lulu Wang, Xue Bai, Tingting Bu, Jie Zhang, Ming Lu, Nam-Chul Ha, Chunshan Quan, Ki Hyun Nam and Yongbin Xu

Molecules 2022, 27(15), 4781; https://doi.org/10.3390/molecules27154781 - 26 Jul 2022

Cited by 2 | Viewed by 2001

Abstract

Pyridoxal 5′-phosphate (PLP) is the active form of vitamin B6, but it is highly reactive and poisonous in its free form. YggS is a PLP-binding protein found in bacteria and humans that mediates PLP homeostasis by delivering PLP to target enzymes or by [...] Read more.

Pyridoxal 5′-phosphate (PLP) is the active form of vitamin B6, but it is highly reactive and poisonous in its free form. YggS is a PLP-binding protein found in bacteria and humans that mediates PLP homeostasis by delivering PLP to target enzymes or by performing a protective function. Several biochemical and structural studies of YggS have been reported, but the mechanism by which YggS recognizes PLP has not been fully elucidated. Here, we report a functional and structural analysis of YggS from Fusobacterium nucleatum (FnYggS). The PLP molecule could bind to native FnYggS, but no PLP binding was observed for selenomethionine (SeMet)-derivatized FnYggS. The crystal structure of FnYggS showed a type III TIM barrel fold, exhibiting structural homology with several other PLP-dependent enzymes. Although FnYggS exhibited low (<35%) amino acid sequence similarity with previously studied YggS proteins, its overall structure and PLP-binding site were highly conserved. In the PLP-binding site of FnYggS, the sulfate ion was coordinated by the conserved residues Ser201, Gly218, and Thr219, which were positioned to provide the binding moiety for the phosphate group of PLP. The mutagenesis study showed that the conserved Ser201 residue in FnYggS was the key residue for PLP binding. These results will expand the knowledge of the molecular properties and function of the YggS family. Full article

(This article belongs to the Special Issue Protein Structure, Function and Interaction)

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Review

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16 pages, 4109 KiB

Open AccessReview

Thymosin α1 and Its Role in Viral Infectious Diseases: The Mechanism and Clinical Application

by Nana Tao, **e Xu, Yuyuan Ying, Shiyu Hu, Qingru Sun, Guiyuan Lv and Jianli Gao

Molecules 2023, 28(8), 3539; https://doi.org/10.3390/molecules28083539 - 17 Apr 2023

Cited by 10 | Viewed by 5011

Abstract

Thymosin α1 (Tα1) is an immunostimulatory peptide that is commonly used as an immune enhancer in viral infectious diseases such as hepatitis B, hepatitis C, and acquired immune deficiency syndrome (AIDS). Tα1 can influence the functions of immune cells, such as T cells, [...] Read more.

Thymosin α1 (Tα1) is an immunostimulatory peptide that is commonly used as an immune enhancer in viral infectious diseases such as hepatitis B, hepatitis C, and acquired immune deficiency syndrome (AIDS). Tα1 can influence the functions of immune cells, such as T cells, B cells, macrophages, and natural killer cells, by interacting with various Toll-like receptors (TLRs). Generally, Tα1 can bind to TLR3/4/9 and activate downstream IRF3 and NF-κB signal pathways, thus promoting the proliferation and activation of target immune cells. Moreover, TLR2 and TLR7 are also associated with Tα1. TLR2/NF-κB, TLR2/p38MAPK, or TLR7/MyD88 signaling pathways are activated by Tα1 to promote the production of various cytokines, thereby enhancing the innate and adaptive immune responses. At present, there are many reports on the clinical application and pharmacological research of Tα1, but there is no systematic review to analyze its exact clinical efficacy in these viral infectious diseases via its modulation of immune function. This review offers an overview and discussion of the characteristics of Tα1, its immunomodulatory properties, the molecular mechanisms underlying its therapeutic effects, and its clinical applications in antiviral therapy. Full article

(This article belongs to the Special Issue Protein Structure, Function and Interaction)

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28 pages, 8551 KiB

Open AccessReview

Molecular Mechanisms and Applications of N-Acyl Homoserine Lactone-Mediated Quorum Sensing in Bacteria

by Lokender Kumar, Sanjay Kumar Singh Patel, Kusum Kharga, Rajnish Kumar, Pradeep Kumar, Jessica Pandohee, Sourabh Kulshresha, Kusum Harjai and Sanjay Chhibber

Molecules 2022, 27(21), 7584; https://doi.org/10.3390/molecules27217584 - 4 Nov 2022

Cited by 31 | Viewed by 4753

Abstract

Microbial biodiversity includes biotic and abiotic components that support all life forms by adapting to environmental conditions. Climate change, pollution, human activity, and natural calamities affect microbial biodiversity. Microbes have diverse growth conditions, physiology, and metabolism. Bacteria use signaling systems such as quorum [...] Read more.

Microbial biodiversity includes biotic and abiotic components that support all life forms by adapting to environmental conditions. Climate change, pollution, human activity, and natural calamities affect microbial biodiversity. Microbes have diverse growth conditions, physiology, and metabolism. Bacteria use signaling systems such as quorum sensing (QS) to regulate cellular interactions via small chemical signaling molecules which also help with adaptation under undesirable survival conditions. Proteobacteria use acyl-homoserine lactone (AHL) molecules as autoinducers to sense population density and modulate gene expression. The LuxI-type enzymes synthesize AHL molecules, while the LuxR-type proteins (AHL transcriptional regulators) bind to AHLs to regulate QS-dependent gene expression. Diverse AHLs have been identified, and the diversity extends to AHL synthases and AHL receptors. This review comprehensively explains the molecular diversity of AHL signaling components of Pseudomonas aeruginosa, Chromobacterium violaceum, Agrobacterium tumefaciens, and Escherichia coli. The regulatory mechanism of AHL signaling is also highlighted in this review, which adds to the current understanding of AHL signaling in Gram-negative bacteria. We summarize molecular diversity among well-studied QS systems and recent advances in the role of QS proteins in bacterial cellular signaling pathways. This review describes AHL-dependent QS details in bacteria that can be employed to understand their features, improve environmental adaptation, and develop broad biomolecule-based biotechnological applications. Full article

(This article belongs to the Special Issue Protein Structure, Function and Interaction)

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