Proteins-Structure Function and Bioinformatics最新文献_第3页

Crucial Role of an Additional α1-α3 Salt Bridge in Stabilizing the Active Site of Sphingomonas sp. Glutaredoxin 3 for Cold Adaptation. 额外α1-α3盐桥在稳定鞘氨单胞菌Glutaredoxin 3冷适应活性位点中的重要作用

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-17 DOI: 10.1002/prot.70001

Hoa Nguyen, Trang Van Tran, Tu Anh Nguyen, ChangWoo Lee

{"title":"Crucial Role of an Additional α1-α3 Salt Bridge in Stabilizing the Active Site of Sphingomonas sp. Glutaredoxin 3 for Cold Adaptation.","authors":"Hoa Nguyen, Trang Van Tran, Tu Anh Nguyen, ChangWoo Lee","doi":"10.1002/prot.70001","DOIUrl":"https://doi.org/10.1002/prot.70001","url":null,"abstract":"Bacterial glutaredoxin 3 (Grx3) proteins are class I oxidoreductases with a canonical thioredoxin fold. They maintain a conserved glutathione (GSH) interaction site across a range of temperatures, yet their cold adaptation mechanisms remain largely unexplored. In mesophilic Escherichia coli Grx3 (EcGrx3), two conserved α3-helix salt bridges are present, whereas psychrophilic Sphingomonas sp. Grx3 (SpGrx3) features an additional α1-α3 salt bridge (Arg17-Asp68) that is absent in EcGrx3, where Tyr69 occupies the equivalent position. This study investigates how SpGrx3 stabilizes its active site during cold adaptation, focusing on α3-helix salt bridges and aromatic residues. We show that disrupting the C-terminal salt bridge (Lys25 with Glu74-Asp80, between α1-α3) reduces thermal and thermodynamic stability, while disrupting the N-terminal salt bridges (Arg17-Asp68 between α1-α3 and Arg51-Asp69 between α2-α3) diminishes GSH affinity. Substituting α3-helix aromatic residues in SpGrx3 (S67F, S67Y, and A71Y) to mimic the EcGrx3 configuration improves both thermal stability and GSH affinity, whereas the Y69A mutation in EcGrx3-a reciprocal substitution of A71Y in SpGrx3-reduces these properties. These results indicate that Tyr69 is critical for active-site stability in EcGrx3, while its absence in SpGrx3 leads to increased flexibility and reduced GSH affinity, which is partially compensated by the formation of an additional α1-α3 salt bridge during cold adaptation. This study highlights the essential role of α1-α3 helix interactions in preserving the oxidoreductase function of Grx3 proteins across varying temperatures.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Crystal Structure and Functional Characterization of YjgK From Salmonella Typhimurium. 鼠伤寒沙门菌YjgK晶体结构及功能表征

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-17 DOI: 10.1002/prot.26854

Su-Yeon Choi, Eunsuk Kim, Hyunjin Yoon, Ha-Neul Kim, Ji-Hun Kim, Seung-Hyeon Seok, Min-Duk Seo

{"title":"Crystal Structure and Functional Characterization of YjgK From Salmonella Typhimurium.","authors":"Su-Yeon Choi, Eunsuk Kim, Hyunjin Yoon, Ha-Neul Kim, Ji-Hun Kim, Seung-Hyeon Seok, Min-Duk Seo","doi":"10.1002/prot.26854","DOIUrl":"https://doi.org/10.1002/prot.26854","url":null,"abstract":"The YhcH/YjgK/YiaL (DUF386) family, widely conserved across bacterial species, is involved in essential cellular processes yet remains poorly characterized. YjgK from Salmonella enterica serovar Typhimurium has drawn attention because of its potential role in biofilm formation associated with metal homeostasis, which may be critical for bacterial survival. In this study, we report the crystal structure of YjgK at 1.76 Å resolution, revealing a dimeric arrangement where each monomer consists of a jelly roll-type β-sandwich fold. This fold forms a funnel-shaped cavity, suggesting potential ligand binding. YjgK contains two zinc ions per dimer, which were identified through structural analysis and confirmed by inductively coupled plasma mass spectrometry (ICP-MS). The zinc ions are coordinated by conserved residues (Glu62, His64, Asp69, and His128) to form a tetrahedral geometry. Structural comparisons with homologous proteins revealed significant similarities in their overall fold but distinct differences in their metal ion specificity, with YhcH binding copper and HP1029 binding zinc. Salmonella lacking YjgK increased biofilm formation, while YjgK overexpression hardly influenced biofilm formation. Our findings suggest that the zinc-binding capability of YjgK may play a key role in metal ion homeostasis, contributing to the ability of Salmonella to form biofilm in response to metal-limited environments, such as those encountered during infection. The conservation of DUF386 fold across species, along with variations in metal ion coordination, indicates functional diversification within this family.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In Vitro Amyloid Formation by a Bacteriocin From Bifidobacterium longum subsp. infantis. 长双歧杆菌细菌素体外淀粉样蛋白形成的研究。对象的。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-17 DOI: 10.1002/prot.70002

Ayane Kumagai, Kouta Mayanagi, Seiichiro Hayashi, Shogo Nakano, Sohei Ito, Daisuke Fujinami

{"title":"In Vitro Amyloid Formation by a Bacteriocin From Bifidobacterium longum subsp. infantis.","authors":"Ayane Kumagai, Kouta Mayanagi, Seiichiro Hayashi, Shogo Nakano, Sohei Ito, Daisuke Fujinami","doi":"10.1002/prot.70002","DOIUrl":"https://doi.org/10.1002/prot.70002","url":null,"abstract":"Bifidobacterium longum subsp. infantis is a probiotic bacterium isolated from human milk-fed infants. This species secretes various metabolites that contribute to gut microbiome development and immune system maturation. In this study, we investigated bacteriocins, ribosomally synthesized peptides that typically exhibit antimicrobial activity. We produced Blon_0434, a B. infantis-derived bacteriocin belonging to the Lactococcin 972 family, by expressing it heterologously in Escherichia coli. Our results demonstrate that recombinant Blon_0434 is secreted via the Sec-dependent pathway but exhibited no detectable antimicrobial activity under the tested conditions. NMR structural analysis suggests that Blon_0434 is thermodynamically unstable, which may account for its inactivity. Unexpectedly, Blon_0434 formed amyloid-like fibrils in vitro, as demonstrated by thioflavin T fluorescence and transmission electron microscopy. The biological implications of Blon_0434 amyloid formation warrant further investigation, particularly regarding microbial interactions and host immune responses.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural and Functional Analysis of Plant Oil-Body Lipase EgLIP1 From Elaeis guineensis. 豚鼠油脂体脂肪酶EgLIP1的结构与功能分析。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-16 DOI: 10.1002/prot.26852

Jia Rong Tey, Siti Fatimah, Maizom Hassan, Anusha Nair, Chyan Leong Ng

{"title":"Structural and Functional Analysis of Plant Oil-Body Lipase EgLIP1 From Elaeis guineensis.","authors":"Jia Rong Tey, Siti Fatimah, Maizom Hassan, Anusha Nair, Chyan Leong Ng","doi":"10.1002/prot.26852","DOIUrl":"https://doi.org/10.1002/prot.26852","url":null,"abstract":"EgLIP1 is an oil-body lipase (EC 3.1.1.3) overexpressed in the fruit mesocarp of Elaeis guineensis (oil palm). Despite its significant role in fruit ripening and the hydrolysis of of triacylglycerol into free fatty acids (FFA) in oil palm, the molecular structure and functional understanding of EgLIP1 are yet to be fully elucidated. Phylogenetic analysis reveals that EgLIP1 shares homology with several plant oil-body lipases. The 3D structure of EgLIP1 was modeled using AlphaFold 2 with high confidence (pLDDT score of 89.7). Structural comparison with Rhizomucor miehei triacylglycerol lipase (RML) reveals that the regions β1, η1, α1, η2, β2, α2, α3, α4, α15, α16, and β15 represent novel insertions unique to EgLIP1, while the overall fold in other regions of the protein remains highly conserved in comparison to RML. Notably, an insertion of residue \"PF\" was also found in EgLIP1 and its plant orthologs. This insertion is located immediately before the lid domain helix, forming a kink facing toward the active lipase site. Enzyme-membrane surface interaction prediction suggests that α1, α3, α4, α15, and α16 are likely involved in anchoring EgLIP1 at the interface of the phospholipid monolayer of oil bodies. Molecular docking and molecular dynamics (MD) simulation analyses of EgLIP1 with its potential substrate, 1-palmitoylglycerol, demonstrate that the catalytic serine residue S308 and the GX oxyanion hole motif residue T223 can form hydrogen bonds with the carbonyl group of the ligand to initiate a nucleophilic attack on the substrate. Our structure-guided functional studies provide molecular insights into how EgLIP1 associates with oil bodies and catalyzes its potential substrates.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Allium sativum-Derived Alliin and Allicin Stably Bind to α-Synuclein and Prevent Its Cytotoxic Aggregation. 葱源大蒜素和大蒜素稳定结合α-突触核蛋白并阻止其细胞毒性聚集。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-14 DOI: 10.1002/prot.70000

S Rehan Ahmad, Md Zeyaullah, Abdullah M AlShahrani, Khursheed Muzammil, Adam Dawria, Md Faruque Ahmad, Ahmed Salih

{"title":"Allium sativum-Derived Alliin and Allicin Stably Bind to α-Synuclein and Prevent Its Cytotoxic Aggregation.","authors":"S Rehan Ahmad, Md Zeyaullah, Abdullah M AlShahrani, Khursheed Muzammil, Adam Dawria, Md Faruque Ahmad, Ahmed Salih","doi":"10.1002/prot.70000","DOIUrl":"https://doi.org/10.1002/prot.70000","url":null,"abstract":"Neurodegenerative diseases such as Parkinson's disease are characterized by the pathological aggregation of α-synuclein. Targeting α-synuclein aggregation through natural bioactive compounds offers a promising therapeutic strategy. In this study, sulfur-containing compounds derived from Allium sativum were evaluated for their drug-likeness, pharmacokinetic properties, and ability to inhibit α-synuclein aggregation using a combination of in silico and in vitro approaches. ADMET profiling indicated high gastrointestinal absorption for nine compounds, supporting their drug-like properties. Six compounds were predicted to cross the blood-brain barrier, suggesting potential efficacy in the central nervous system. Molecular docking identified alliin, allicin, E-ajoene, and diallyl disulfide as top binders to α-synuclein, forming stable interactions with key aggregation-prone regions. Molecular dynamics simulations over 100 ns confirmed the structural stability of alliin- and allicin-α-synuclein complexes, with minimal residue fluctuations and persistent hydrogen bonding. MM-GBSA binding energy analysis corroborated these results, showing favorable binding free energies, particularly for alliin and E-ajoene. Principal component analysis (PCA) further supported the role of alliin in stabilizing α-synuclein dynamics. In vitro cellular assays further validated these computational findings. Using an SH-SY5Y cell-based α-synuclein aggregation model, treatment with alliin and allicin significantly reduced α-synuclein aggregation. Furthermore, MTT-based cytotoxicity assays in SH-SY5Y neuroblastoma cells overexpressing α-synuclein revealed that alliin and allicin conferred notable cytoprotective effects by reducing α-synuclein-induced toxicity. Taken together, these findings highlight alliin and allicin as potent lead compounds that not only bind and stabilize α-synuclein but also attenuate its aggregation and associated cytotoxicity.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancing RNA 3D Structure Prediction in CASP16: Integrating Physics-Based Modeling With Machine Learning for Improved Predictions. 在CASP16中增强RNA 3D结构预测：将基于物理的建模与机器学习集成以改进预测。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-09 DOI: 10.1002/prot.26856

Sicheng Zhang, Jun Li, Yuanzhe Zhou, Shi-Jie Chen

引用次数: 0

Structural Analysis of the SARS-CoV-2 Spike N-Terminal Domain Across Wild-Type and Recent Variants: A Comparative Study. SARS-CoV-2穗n端结构域在野生型和新变体中的结构分析：比较研究

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-09 DOI: 10.1002/prot.26855

Miriana Quaranta, Allegra Via, Stefano Pascarella

{"title":"Structural Analysis of the SARS-CoV-2 Spike N-Terminal Domain Across Wild-Type and Recent Variants: A Comparative Study.","authors":"Miriana Quaranta, Allegra Via, Stefano Pascarella","doi":"10.1002/prot.26855","DOIUrl":"https://doi.org/10.1002/prot.26855","url":null,"abstract":"Since its first appearance in China, the molecular evolution of SARS-CoV-2 has progressed through altering the properties of the Spike protein, changing the virus ability to transmit and to evade host immune surveillance. Despite receiving less attention than the Receptor Binding Domain (RBD), the Spike N-Terminal Domain (NTD) is crucial to SARS-CoV-2 biology and pathogenesis. This study provides a comparative structural analysis of the NTD from the wild-type strain and different variants (BA.2, XBB.1, XBB.1.5, BA.2.86, JN.1, HV.1, KP.2, KP.3, and KP.3.1.1), aiming to clarify the structural impact of mutations in each variant. To assess the impact of mutations on the interaction of NTD with antibodies, we selected as a test case the neutralizing antibody 4A8, which has proven highly effective against the WT. The results obtained from molecular dynamics simulations, surface electrostatic potential analysis, and binding energy predictions show a clear trend in the evolution of the virus. The net charge of the NTD decreases as the variants progress, reaching a minimum charge of -1.84 observed for KP.3.1.1. This is in clear contrast to the RBD net charge, which follows an opposite trend toward higher positive values. Binding energy predictions show that the antibody's efficacy decreases as the virus evolves. While the WT exhibited an interaction energy of -96.28 kcal/mol with 4A8, more recent variants like KP.3 show no interaction stronger than -64.00 kcal/mol. These results reveal a clear trend of modifications aimed at favoring immune escape in the virus' evolutionary trajectory.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modeling CAPRI Targets of Round 55 by Combining AlphaFold and Docking. 结合AlphaFold和对接的第55轮CAPRI目标建模

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-06 DOI: 10.1002/prot.26853

Amar Singh, Matthew M Copeland, Petras J Kundrotas, Ilya A Vakser

{"title":"Modeling CAPRI Targets of Round 55 by Combining AlphaFold and Docking.","authors":"Amar Singh, Matthew M Copeland, Petras J Kundrotas, Ilya A Vakser","doi":"10.1002/prot.26853","DOIUrl":"https://doi.org/10.1002/prot.26853","url":null,"abstract":"In recent years, the field of structural biology has seen remarkable advancements, particularly in modeling of protein tertiary and quaternary structures. The AlphaFold deep learning approach revolutionized protein structure prediction by achieving near-experimental accuracy on many targets. This paper presents a detailed account of structural modeling of oligomeric targets in Round 55 of CAPRI by combining deep learning-based predictions (AlphaFold2 multimer pipeline) with traditional docking techniques in a hybrid approach to protein-protein docking. To complement the AlphaFold models generated for the given oligomeric state of the targets, we built docking predictions by combining models generated for lower-oligomeric states-dimers for trimeric targets and trimers/dimers for tetrameric targets. In addition, we used a template-based docking procedure applied to AlphaFold predicted structures of the monomers. We analyzed the clustering of the generated AlphaFold models, the confidence in the prediction of intra- and inter-chain residue-residue contacts, and the correlation of the AlphaFold predictions stability with the quality of the submitted models.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lysine Acetylation of Plant α-Tubulins: Scaling Up the Local Effect to Large System Transformations. 植物α-微管蛋白赖氨酸乙酰化：放大局部效应到大系统转化。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-04 DOI: 10.1002/prot.26846

Alexey Rayevsky, Elijah Bulgakov, Rostyslav Blume, Dmytro Novozhylov, Mariia Stykhylias, Serhii Ozheredov, Pavlo Karpov, Yaroslav Blume

{"title":"Lysine Acetylation of Plant α-Tubulins: Scaling Up the Local Effect to Large System Transformations.","authors":"Alexey Rayevsky, Elijah Bulgakov, Rostyslav Blume, Dmytro Novozhylov, Mariia Stykhylias, Serhii Ozheredov, Pavlo Karpov, Yaroslav Blume","doi":"10.1002/prot.26846","DOIUrl":"https://doi.org/10.1002/prot.26846","url":null,"abstract":"Cell migration and motility, cell division, biogenesis and renewal of cell and tissue integrity, and the assembly and retention of cell or tissue architecture, to name but a few, represent increasingly vital processes at the cellular and whole-body levels. These biological processes are closely connected with the major structural transformations that cytoskeletal proteins undergo due to numerous post-translational modifications, including acetylation, tyrosynation, polyglutamylation, etc. We collected all the information on tubulin acetylation and data on related cellular manifestations. This work expands upon our previous investigations into PTM-associated microtubule remodeling by incorporating K60, K163, and K326 into our analysis. Subsequently, we applied the refined protocol to examine the impact of acetylation on the most prevalent tubulin isoforms: TBA1, TBA2, and TBA3. Our analysis identified three distinct patterns on the α-tubulin surface where interactions with neighboring subunits were altered upon acetylation. These findings suggest that acetylation significantly influences the inter-subunit interactions within the microtubule polymer. To assess the likelihood of rearrangement at each of the three acetylation sites (K60, K163, K326), we conducted a series of simulations involving nine tubulin molecules (representing a microtubule lattice). These simulations aimed to quantify the degree of dissociation susceptibility upon acetylation at each of these specific lysine residues while focusing on residues that serve as substrates for HDAC6 deacetylation in plants, K60, K163, and K326. In this study, we have gathered all relevant evidence for the impact of different acetylation points on the assembly and lifespan of microtubule organelles, using A. thaliana tubulins as a model object.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of Extracellular Histidine Residues for the Function and pH Sensitivity of Human Organic Anion Transporting Polypeptide 1B3. 细胞外组氨酸残基对人体有机阴离子转运多肽1B3的功能和pH敏感性的作用。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-04 DOI: 10.1002/prot.26851

Wanjun Han, Han Liu, Ting Liang, Lanjing Li, Ru Huan, Chunshan Gui

{"title":"Role of Extracellular Histidine Residues for the Function and pH Sensitivity of Human Organic Anion Transporting Polypeptide 1B3.","authors":"Wanjun Han, Han Liu, Ting Liang, Lanjing Li, Ru Huan, Chunshan Gui","doi":"10.1002/prot.26851","DOIUrl":"https://doi.org/10.1002/prot.26851","url":null,"abstract":"Organic anion transporting polypeptide 1B3 (OATP1B3) is a liver-specific transporter that mediates uptake of various substances from blood into hepatocytes. The transport function of OATP1B3 was shown to be pH-sensitive. As the protonation state of extracellular histidine residues can be affected by the environmental pH, in the present study, the role of 7 extracellular histidine residues in the function and pH sensitivity of OATP1B3 has been examined. Our results showed that H115 had the most significant effect on the function of OATP1B3. The Cryo-EM structure of OATP1B3 indicated that H115 is involved in the binding and release of bicarbonate during a transport cycle. Functional studies on H115 mutants suggested that a hydrogen-bond forming group was preferred over a positively charged group at site 115, indicating that a hydrogen bond is optimum for bicarbonate's binding/release cycle. This may also explain why OATP1B3 showed lower transport function at pH 4.5 than at pH 7.4, as H115 is positively charged at pH 4.5 but neutral at pH 7.4. In addition, the H115A mutation largely compromised the pH sensitivity of OATP1B3, probably due to the loss of its protonation state switching capability. Taken together, H115 plays an important role in the function and pH sensitivity of OATP1B3.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0