Proteins-Structure Function and Bioinformatics最新文献_第2页

Computational Elucidation of Possible Contributors to Formation and Stabilization of ATP-Lid Down-Conformation in the N-Terminal Domain of Hsp90. Hsp90 n端结构域中ATP-Lid - down构象形成和稳定可能因素的计算解析。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-04 DOI: 10.1002/prot.26849

Keigo Gohda

{"title":"Computational Elucidation of Possible Contributors to Formation and Stabilization of ATP-Lid Down-Conformation in the N-Terminal Domain of Hsp90.","authors":"Keigo Gohda","doi":"10.1002/prot.26849","DOIUrl":"https://doi.org/10.1002/prot.26849","url":null,"abstract":"Heat shock protein 90 (Hsp90) controls activation and maturation of various crucial client proteins through a catalytic cycle. In this catalytic cycle, closure of the lid segment from up- to down-conformation in the N-terminal domain (NTD) of Hsp90 through ATP binding is indispensable for coordinated structural changes, including interchange of dimeric Hsp90 structure between open and closed forms. However, the mechanisms underlying lid closure remain unclear. In this study, we investigate structural characteristics of the lid-down conformation in an isolated monomeric NTD structure by two types of molecular-dynamic simulation: a flopping-down simulation for a lid-up conformation using repulsive distance-restraints, and a down-conformation simulation for in silico H1-mutants of NTD with a lid-down conformation. In the flopping-down simulation, spontaneous formation of a lid-down conformation is observed multiple times. K98 and K102 in the lid segment are observed to interact with ATP phosphate or D40, suggesting that they contribute to the formation of the lid-down conformation. In the down-conformation simulation, the H1 structure of the chimera H1-model, which only retains a proper down-conformation among the models for the entire simulation period, covers the lid segment more than that of the X-ray structure. Because the stability of the lid-down conformation was influenced by H1 structures, the H1 segment is suggested to contribute to stabilization of the lid-down conformation. Although no direct experimental data are currently available to confirm these findings, these simulation results do not show large discrepancies with the experimental data and evidence of structural characteristics of the NTD, deduced from previous X-ray and spectroscopic studies.","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":"144217646","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

Improving AlphaFold2- and AlphaFold3-Based Protein Complex Structure Prediction With MULTICOM4 in CASP16. 利用MULTICOM4改进CASP16中基于AlphaFold2和alphafold3的蛋白复合体结构预测。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-02 DOI: 10.1002/prot.26850

Jian Liu, Pawan Neupane, Jianlin Cheng

{"title":"Improving AlphaFold2- and AlphaFold3-Based Protein Complex Structure Prediction With MULTICOM4 in CASP16.","authors":"Jian Liu, Pawan Neupane, Jianlin Cheng","doi":"10.1002/prot.26850","DOIUrl":"https://doi.org/10.1002/prot.26850","url":null,"abstract":"With AlphaFold achieving high-accuracy tertiary structure prediction for most single-chain proteins (monomers), the next major challenge in protein structure prediction is to accurately model multichain protein complexes (multimers). We developed MULTICOM4, the latest version of the MULTICOM system, to improve protein complex structure prediction by integrating transformer-based AlphaFold2, diffusion model-based AlphaFold3, and our in-house techniques. These include protein complex stoichiometry prediction, diverse multiple sequence alignment (MSA) generation leveraging both sequence and structure comparison, modeling exception handling, and deep learning-based protein model quality assessment. MULTICOM4 was blindly evaluated in the 16th Critical Assessment of Techniques for Protein Structure Prediction (CASP16) in 2024. In Phase 0 of CASP16, where stoichiometry information was unavailable, MULTICOM predictors performed best, with MULTICOM_human achieving a TM-score of 0.752 and a DockQ score of 0.584 for top-ranked predictions on average. In Phase 1 of CASP16, with stoichiometry information provided, MULTICOM_human remained among the top predictors, attaining a TM-score of 0.797 and a DockQ score of 0.558 on average. The CASP16 results demonstrate that integrating complementary AlphaFold2 and AlphaFold3 with enhanced MSA inputs, comprehensive model ranking, exception handling, and accurate stoichiometry prediction can effectively improve protein complex structure prediction.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200947","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

The Pseudoenzyme β-Amylase9 From Arabidopsis Activates α-Amylase3: A Possible Mechanism to Promote Stress-Induced Starch Degradation. 拟南芥β-淀粉酶9激活α-淀粉酶3：促进应激诱导淀粉降解的可能机制

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-01 Epub Date: 2025-01-23 DOI: 10.1002/prot.26803

Christopher E Berndsen, Amanda R Storm, Angelina M Sardelli, Sheikh R Hossain, Kristen R Clermont, Luke M McFather, Mafe A Connor, Jonathan D Monroe

{"title":"The Pseudoenzyme β-Amylase9 From Arabidopsis Activates α-Amylase3: A Possible Mechanism to Promote Stress-Induced Starch Degradation.","authors":"Christopher E Berndsen, Amanda R Storm, Angelina M Sardelli, Sheikh R Hossain, Kristen R Clermont, Luke M McFather, Mafe A Connor, Jonathan D Monroe","doi":"10.1002/prot.26803","DOIUrl":"10.1002/prot.26803","url":null,"abstract":"Starch accumulation in plants provides carbon for nighttime use, for regrowth after periods of dormancy, and for times of stress. Both ɑ- and β-amylases (AMYs and BAMs, respectively) catalyze starch hydrolysis, but their functional roles are unclear. Moreover, the presence of catalytically inactive amylases that show starch excess phenotypes when deleted presents questions on how starch degradation is regulated. Plants lacking one of these catalytically inactive β-amylases, BAM9, have enhanced starch accumulation when combined with mutations in BAM1 and BAM3, the primary starch degrading BAMs in response to stress and at night, respectively. BAM9 has been reported to be transcriptionally induced by stress although the mechanism for BAM9 function is unclear. From yeast two-hybrid experiments, we identified the plastid-localized AMY3 as a potential interaction partner for BAM9. We found that BAM9 interacted with AMY3 in vitro and that BAM9 enhances AMY3 activity about three-fold. Modeling of the AMY3-BAM9 complex predicted a previously undescribed alpha-alpha hairpin in AMY3 that could serve as a potential interaction site. Additionally, AMY3 lacking the alpha-alpha hairpin is unaffected by BAM9. Structural analysis of AMY3 showed that it can form a homodimer in solution and that BAM9 appears to replace one of the AMY3 monomers to form a heterodimer. The presence of both BAM9 and AMY3 in many vascular plant lineages, along with model-based evidence that they heterodimerize, suggests that the interaction is conserved. Collectively these data suggest that BAM9 is a pseudoamylase that activates AMY3 in response to cellular stress, possibly facilitating stress recovery.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1189-1201"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decoding the Torsional Dynamics of Main-Chain Atoms Within CαNN Motif Facilitating Specific Anion Recognition. 解码c - α nn基序中主链原子的扭转动力学，促进特定阴离子识别。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-01 Epub Date: 2025-01-07 DOI: 10.1002/prot.26798

Akash Roy, Vinith Johnson, Pramiti Das, Shuvam Paul, Subhankar Sahu, Raja Banerjee

{"title":"Decoding the Torsional Dynamics of Main-Chain Atoms Within CαNN Motif Facilitating Specific Anion Recognition.","authors":"Akash Roy, Vinith Johnson, Pramiti Das, Shuvam Paul, Subhankar Sahu, Raja Banerjee","doi":"10.1002/prot.26798","DOIUrl":"10.1002/prot.26798","url":null,"abstract":"The structural plasticity of proteins at the molecular level is largely dictated by backbone torsion angles, which play a critical role in ligand recognition and binding. To establish the anion-induced cooperative arrangement of the main-chain (mc) torsion, herein, we analyzed a set of naturally occurring CαNN motifs as \"static models\" for their anion-binding competence through docking and molecular dynamics simulations and decoded its torsion angle influenced mc-driven anion recognition potential. By comparing a pool of 20 distinct sets of CαNN motif with identical sequences in their \"anion bound/present, aP\" and \"anion free/absent, aA\" versions, we could discern that there exists a positive correlation between the \"difference of anion residence time (ΔRT)\" and \"difference among the main-chain torsion angle\" of the aP and aA population. Notably, the anion interaction with CαNNs is locally energetically favorable even in a context-free non-proteinaceous environment and if the difference of the mc-torsion angles involving the Cα-1, N0, N1 residues for a population is higher between the aP and aA state, the difference among the ligand RT is also greater. At the atomistic level, the accommodation of anion is highly synergistic and cooperatively sways the interacting mc-atom torsions. By comparing the clustering of H-bonding patterns, the free energy of binding, and RT in both states, we provide evidence that to establish favorable thermodynamics and kinetics of ligand accommodation in these short structural motifs, proper reorientation of local-mc governed by torsions is a prerequisite. Our findings position the CαNN motif as a promising scaffold for peptidomimetic design and emphasize the critical role of loop region dynamics in protein structure-function relationships.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1107-1117"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959665","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

Probing Enzymatic Acetylation Events in Real Time With NMR Spectroscopy: Insights Into Acyl-Cofactor Dependent p300 Modification of Histone H4. 用核磁共振光谱实时探测酶乙酰化事件：对酰基辅助因子依赖的p300修饰组蛋白H4的见解。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-01 DOI: 10.1002/prot.26848

Sophia M Dewing, Scott A Showalter

{"title":"Probing Enzymatic Acetylation Events in Real Time With NMR Spectroscopy: Insights Into Acyl-Cofactor Dependent p300 Modification of Histone H4.","authors":"Sophia M Dewing, Scott A Showalter","doi":"10.1002/prot.26848","DOIUrl":"https://doi.org/10.1002/prot.26848","url":null,"abstract":"Lysine acylation is a rapidly expanding class of post-translational modifications with largely unexplored functional roles; the study of acylations beyond acetylation is especially impeded by limited methods for their preparation, detection, and characterization in vitro. We previously reported a nuclear magnetic resonance (NMR)-based approach to monitor Nε-lysine acetylation following Ada2/Gcn5-catalyzed installation of a 13C-acetyl probe on the histone H3 tail. Building on this foundation, here we expand those techniques by demonstrating the installation and 1H, 13C-HSQC based NMR detection of both 13C-acetyl and 13C-propionyl probes on the histone H4 tail using a mutant p300 lysine acetyltransferase (KAT) enzyme with enhanced activity. Additionally, we introduce a continuous evaluation method for acyltransferase reaction data, enabling the extraction of relative rate constants-a technique inspired by our laboratory's recent work on NMR methyltransferase kinetics. This study demonstrates that our NMR-based approach to assay enzymatic 13C-acylation is adaptable, providing a versatile platform for investigating a range of acylations, KAT enzymes, and protein substrates. Notably, in the process of developing these methods, we observed that p300 KAT may display distinct modification site preferences and regulatory mechanisms depending on the acyl cofactor utilized, underscoring the method's potential to advance the emerging field of lysine acylation biochemistry.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200948","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

Exploring the Effect of Hydrocarbon Cross-Linkers on the Structure and Binding of Stapled p53 Peptides. 探索碳氢化合物交联剂对订书钉 p53 肽的结构和结合的影响。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-01 Epub Date: 2025-01-03 DOI: 10.1002/prot.26793

Asha Rani Choudhury, Vikram Gaikwad, Atanu Maity, Rajarshi Chakrabarti

{"title":"Exploring the Effect of Hydrocarbon Cross-Linkers on the Structure and Binding of Stapled p53 Peptides.","authors":"Asha Rani Choudhury, Vikram Gaikwad, Atanu Maity, Rajarshi Chakrabarti","doi":"10.1002/prot.26793","DOIUrl":"10.1002/prot.26793","url":null,"abstract":"Short-length peptides are used as therapeutics due to their high target specificity and low toxicity; for example, peptides are designed for targeting the interaction between oncogenic protein p53 and E3 ubiquitin ligase MDM2. These peptide therapeutics form a class of successful inhibitors. To design such peptide-based inhibitors, stapling is one of the methods in which amino acid side chains are stitched together to get conformationally rigid peptides, ensuring effective binding to their partners. In the current work, we use computer simulations to investigate p53 peptides stapled with hydrocarbon chains of different lengths and positions of attachment to the peptide. We subsequently analyze their binding efficiency with MDM2. The introduction of stapling agents restricts the conformational dynamics of peptides, resulting in higher persistence of helicity. The efficiency of the stapling agents has also been verified imposing these stapled peptides to adverse conditions viz. thermal and chemical denaturation. In addition, the conformational exploration of peptides has been investigated using temperature replica exchange molecular dynamics (T-REMD) simulations. From both the unbiased and T-REMD simulations, p53 with a long hydrocarbon cross-linker shows a more conformationally rigid structure having high helicity compared to other stapled peptides. The rigidity gained due to cross-linking reduces the entropy of the peptide in the free state and thereby facilitates the complexation process. From the binding studies, we have shown that the peptide having multiple short staples has a larger enthalpy change during binding, resulting from its orientation and interactions with residues in the binding interface. On the other hand, a peptide with a single long stapling agent shows less entropic penalty than other systems. Our study suggests a plausible rationale for the relation between the length and the position of attachment of cross-linkers to peptides and their binding affinity for target partners.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1090-1106"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928830","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

High-Throughput Evaluation of Natural Diversity of F-Type ATP Synthase Rotor Ring Stoichiometries. f型ATP合成酶旋翼环化学计量学自然多样性的高通量评价。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-01 Epub Date: 2025-01-15 DOI: 10.1002/prot.26790

Stepan D Osipov, Egor V Zinovev, Arina A Anuchina, Alexander S Kuzmin, Andronika V Minaeva, Yury L Ryzhykau, Alexey V Vlasov, Ivan Yu Gushchin

{"title":"High-Throughput Evaluation of Natural Diversity of F-Type ATP Synthase Rotor Ring Stoichiometries.","authors":"Stepan D Osipov, Egor V Zinovev, Arina A Anuchina, Alexander S Kuzmin, Andronika V Minaeva, Yury L Ryzhykau, Alexey V Vlasov, Ivan Yu Gushchin","doi":"10.1002/prot.26790","DOIUrl":"10.1002/prot.26790","url":null,"abstract":"Adenosine triphosphate (ATP) synthases are large enzymes present in every living cell. They consist of a transmembrane and a soluble domain, each comprising multiple subunits. The transmembrane part contains an oligomeric rotor ring (c-ring), whose stoichiometry defines the ratio between the number of synthesized ATP molecules and the number of ions transported through the membrane. Currently, c-rings of F-Type ATP synthases consisting of 8-17 (except 16) subunits have been experimentally demonstrated, but it is not known whether other stoichiometries are present in natural organisms. Here, we present an easy-to-use high-throughput computational approach based on AlphaFold that allows us to estimate the stoichiometry of all homo-oligomeric c-rings, whose sequences are present in genomic databases. We validate the approach on the available experimental data, obtaining the correlation as high as 0.94 for the reference dataset and use it to predict the existence of c-rings with stoichiometry varying at least from 8 to 27. We then conduct molecular dynamics simulations of two c-rings with stoichiometry above 17 to corroborate the machine learning-based predictions. Our work strongly suggests existence of rotor rings with previously undescribed high stoichiometry in natural organisms and highlights the utility of AlphaFold-based approaches for studying homo-oligomeric proteins.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1128-1140"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985758","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

Sucrose and Gibberellic Acid Binding Stabilize the Inward-Open Conformation of AtSWEET13: A Molecular Dynamics Study. 蔗糖和赤霉素酸结合稳定AtSWEET13内向开放构象：分子动力学研究。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-01 Epub Date: 2025-01-15 DOI: 10.1002/prot.26799

Zoltan Palmai

{"title":"Sucrose and Gibberellic Acid Binding Stabilize the Inward-Open Conformation of AtSWEET13: A Molecular Dynamics Study.","authors":"Zoltan Palmai","doi":"10.1002/prot.26799","DOIUrl":"10.1002/prot.26799","url":null,"abstract":"In plants, sugar will eventually be exported transporters (SWEETs) facilitate the translocation of mono- and disaccharides across membranes and play a critical role in modulating responses to gibberellin (GA3), a key growth hormone. However, the dynamic mechanisms underlying sucrose and GA3 binding and transport remain elusive. Here, we employed microsecond-scale molecular dynamics (MD) simulations to investigate the influence of sucrose and GA3 binding on SWEET13 transporter motions. While sucrose exhibits high flexibility within the binding pocket, GA3 remains firmly anchored in the central cavity. Binding of both ligands increases the average channel radius along the transporter's principal axis. In contrast to the apo form, which retains its initial conformation throughout the simulation, ligand-bound complexes undergo a significant conformational transition characterized by further opening of the intracellular gate relative to the inward-open crystal structure (5XPD). This opening is driven by ligand-induced bending of helix V, stabilizing the inward-open state. Sucrose binding notably enhances the flexibility of the intracellular gate and amplifies anticorrelated motions between the N- and C-terminal domains at the intracellular side, suggesting an opening-closing motion of these domains. Principal component analysis revealed that this gating motion is most pronounced in the sucrose complex and minimal in the apo form, highlighting sucrose's ability to induce high-amplitude gating. Our binding free energy calculations indicate that SWEET13 has lower binding affinity for sucrose compared to GA3, consistent with its role in sugar transport. These results provide insight into key residues involved in sucrose and GA3 binding and transport, advancing our understanding of SWEET13 dynamics.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"1141-1156"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017148","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

Structure, Oligomerization, and Thermal Stability of a Recently Discovered Old Yellow Enzyme. 一种新发现的古老黄色酶的结构、寡聚和热稳定性。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-06-01 Epub Date: 2025-01-22 DOI: 10.1002/prot.26800

Nakia Polidori, Peter Babin, Bastian Daniel, Karl Gruber

引用次数: 0