Biophysical journal最新文献_第2页

Milestone for the interpretation of muscle X-ray diffraction patterns. 肌肉x射线衍射图谱的里程碑。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-09-30 DOI: 10.1016/j.bpj.2025.09.046

Anthony L Hessel

引用次数: 0

Tool antibody fragments reveal multiple conformations of the rhodopsin-Gi signaling complex. Tool抗体片段揭示了视紫红质- gi信号复合物的多种构象。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-09-29 DOI: 10.1016/j.bpj.2025.09.044

Filip Pamula,Oliver Tejero,Jonas Mühle,Ralf Thoma,Gebhard F X Schertler,Jacopo Marino,Ching-Ju Tsai

引用次数: 0

Calcium dynamics in small spaces: lessons learned from modeling in dendritic spines. 小空间中的钙动力学：树突棘建模的经验教训。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-09-29 DOI: 10.1016/j.bpj.2025.09.038

K J McCabe,M Hernández Mesa,P Rangamani

引用次数: 0

Selective Detection of a Key Region in Chemotaxis Signaling Protein Complexes by Solid-State NMR. 固态核磁共振选择性检测趋化信号蛋白复合物关键区域。

IF 3.1 3区生物学

Biophysical journal Pub Date : 2025-09-27 DOI: 10.1016/j.bpj.2025.09.040

Jessica J Allen, Songlin Wang, Chad M Rienstra, Lynmarie K Thompson

{"title":"Selective Detection of a Key Region in Chemotaxis Signaling Protein Complexes by Solid-State NMR.","authors":"Jessica J Allen, Songlin Wang, Chad M Rienstra, Lynmarie K Thompson","doi":"10.1016/j.bpj.2025.09.040","DOIUrl":"10.1016/j.bpj.2025.09.040","url":null,"abstract":"Understanding how large protein complexes function requires tools that can resolve both structure and dynamics in their native assembly states. Here, we apply solid-state NMR (SSNMR) to selectively detect rigid regions of a receptor protein fragment in the context of the >500 kDa chemoreceptor signaling complex found in chemotactic bacteria. These complexes assemble into hexagonal arrays that network multiple active units together. The cytoplasmic fragment of the E. coli aspartate chemoreceptor exhibits dynamics on multiple timescales across different regions of the protein, and these dynamics differ between signaling states. We apply 13C-15N dipolar coupling-based SSNMR experiments to selectively probe the rigid portion (motions slower than millisecond timescale) of this protein, in the context of the full array structure. We optimized assembly methods to form native-like, homogeneous complexes capable of maintaining activity and sample integrity during extended NMR experiments with low electric-field NMR probe designs. A subset of the protein, approximately 100 residues at the membrane-distal tip of the chemoreceptor where it interacts with its associated kinase, was detected and identified as the most rigid region. Chemical shift changes for many residues in this rigid region were observed between NMR spectra of the kinase-on and kinase-off signaling states. This suggests conformational changes occur at the chemoreceptor tip during signaling, which have not been observed in previous studies of this system. These findings demonstrate a dynamics-based NMR spectral editing approach to selectively examine a key region of a large signaling protein within its macromolecular assembly.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Packing of apolar amino acids is not a strong stabilizing force in transmembrane helix dimerization. 在跨膜螺旋二聚化过程中，极性氨基酸的包装并不是一个强大的稳定力。

IF 3.1 3区生物学

Biophysical journal Pub Date : 2025-09-25 DOI: 10.1016/j.bpj.2025.09.036

Gilbert J Loiseau, Alessandro Senes

{"title":"Packing of apolar amino acids is not a strong stabilizing force in transmembrane helix dimerization.","authors":"Gilbert J Loiseau, Alessandro Senes","doi":"10.1016/j.bpj.2025.09.036","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.036","url":null,"abstract":"The factors that stabilize the folding and oligomerization of membrane proteins are still not well understood. In particular, it remains unclear how the tight and complementary packing between apolar side chains observed in the core of membrane proteins contributes to their stability. Complementary packing is a necessary feature since packing defects are generally destabilizing for membrane proteins. The question is the extent by which packing of apolar side chains - and the resulting van der Waals interactions - are a sufficient driving force for stabilizing the interaction between transmembrane helices in the absence of hydrogen bonding and polar interactions. We addressed this question with an approach based on high-throughout protein design and the homodimerization of single-pass helices as the model system. We designed hundreds of transmembrane helix dimers mediated by apolar packing in the backbone configurations that are most commonly found in membrane proteins. We assessed the association propensity of the designs in the membrane of Escherichia coli and found that they were most often monomeric or, at best, weakly dimeric. Conversely, a set of controls designed in the backbone configuration of the GASright motif, which is mediated by weak hydrogen bonds, displayed significantly higher dimerization propensity. The data suggest that packing of apolar side chains and van der Waals interactions may be a relatively weak force in driving transmembrane helix dimerization, unless highly optimized. It also confirms that GASright is a special configuration for achieving stability in membrane proteins.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Reorganization of DNA loops by competition between condensin I and a linker histone. 通过凝聚蛋白I和连接组蛋白之间的竞争重组DNA环。

IF 3.1 3区生物学

Biophysical journal Pub Date : 2025-09-24 DOI: 10.1016/j.bpj.2025.09.002

Tetsuya Yamamoto, Keishi Shintomi, Tatsuya Hirano

{"title":"Reorganization of DNA loops by competition between condensin I and a linker histone.","authors":"Tetsuya Yamamoto, Keishi Shintomi, Tatsuya Hirano","doi":"10.1016/j.bpj.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.002","url":null,"abstract":"Condensin-mediated loop extrusion is thought to be one of the primary mechanisms underlying mitotic chromosome assembly. However, how this process is affected by other chromosomal proteins, such as histones, is not well understood. Our previous study showed that in Xenopus egg extracts codepleted of topoisomerase IIα and the histone chaperone Asf1, a highly characteristic chromatin structure called the \"sparkler\" is assembled. The sparkler is a compact structure assembled on nucleosome-free, entangled DNA in which multiple protrusions radiate from a core. Interestingly, condensin I is concentrated at the tips of the protrusions, whereas the linker histone H1.8 is enriched in the remaining regions of the structure. To understand the biophysical mechanisms underlying sparkler assembly, we construct a model predicting that DNA loops extruded from the entangled DNA undergo phase separation into two domains: loops enriched in condensin I remain as protrusions, whereas those enriched in H1.8 are reeled into the central region. We propose that H1.8 competes with condensin I for DNA binding, thereby reorganizing DNA loops formed by condensin I under this specialized condition.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Diverse Conformational Ensembles Define the Shared Folding-Allosteric Landscapes of Protein Kinases. 不同的构象集合定义了蛋白激酶共享的折叠-变构景观。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-09-24 DOI: 10.1016/j.bpj.2025.09.035

Dhruv Kumar Chaurasiya,Athi N Naganathan

{"title":"Diverse Conformational Ensembles Define the Shared Folding-Allosteric Landscapes of Protein Kinases.","authors":"Dhruv Kumar Chaurasiya,Athi N Naganathan","doi":"10.1016/j.bpj.2025.09.035","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.035","url":null,"abstract":"Sequence variation across members of an enzyme family contributes to diverse ensemble behaviors, which subtly influence substrate affinity, selectivity and regulation. A classic example is the family of eukaryotic protein kinases (EPKs), which regulate numerous cellular processes and serve as important drug targets. Here, we dissect the consequences of sequence variation on the folding-conformational landscapes by performing a meta-analysis of 274 EPKs through a structure-based statistical mechanical framework. We find that EPKs populate several partially structured states in their native ensemble with a hierarchy of structural order in the N-terminal lobe that is critical for catalysis and activation. Despite this, the (un)folding mechanism is uniquely conserved across the majority of kinases, with the N-terminal lobe unfolding first. Kinase activation modulates the local stability and thermodynamic connectivity in a non-conserved manner and across the entire structure, due to the strong coupling between the active site residues to distant sites, including the established allosteric pockets. We further show how activation drives the Abl kinase ensemble towards a more folded and thermodynamically coupled system in a graded manner. Our work uncovers the thermodynamic design principles of kinases with insights into allostery, while shedding light on the extents to which ensemble behaviors are impacted by sequence variations in paralogs.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"61 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

SAXS Assistant: Automated SAXS Analysis for Structural Discovery in Biologics and Polymeric Nanoparticles. SAXS助手：生物制剂和聚合物纳米颗粒结构发现的自动SAXS分析。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-09-24 DOI: 10.1016/j.bpj.2025.09.034

Cesar Ramirez,Elena Di Mare,James Byrnes,Eman Ahmed,Maria Pineiro-Goncalves,Cristian Lopez,N Sanjeeva Murthy,Adam J Gormley

{"title":"SAXS Assistant: Automated SAXS Analysis for Structural Discovery in Biologics and Polymeric Nanoparticles.","authors":"Cesar Ramirez,Elena Di Mare,James Byrnes,Eman Ahmed,Maria Pineiro-Goncalves,Cristian Lopez,N Sanjeeva Murthy,Adam J Gormley","doi":"10.1016/j.bpj.2025.09.034","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.034","url":null,"abstract":"Small-angle X-ray scattering (SAXS) is a powerful technique for assessing macromolecular structure. High-throughput SAXS is limited by the time-consuming and, at times, subjective nature of SAXS data interpretation. We present SAXS Assistant, a Python-based script that streamlines SAXS data analysis to extract features for machine learning (ML) and key structural parameters, including the Guinier radius of gyration (Rg), pair distance distribution function (PDDF)-derived Rg, maximum particle dimension (Dmax), and Kratky plots. The script builds upon BioXTAS RAW, and validates reliability via Guinier/PDDF Rg agreement, an important indicator of well-measured datasets. For assistance in Dmax estimation, a multi-layer perceptron (MLP) regressor was trained with 1,940 data files from the small angle scattering biological data bank (SASBDB). The model achieved a test set performance R2 = 0.90 and mean absolute error (MAE) = 11.7 Å. Training exclusively with experimental data translates analyses from researchers, including experts in the field, to the ML model, which helps assess Dmax estimations from PDDF. Gaussian mixture model (GMM) clustering was implemented to classify profiles into structural classes based on entries in the SASBDB. Users may therefore assess the similarity between experimental samples and known biomolecular shapes within the mapped repository entries. This probabilistic clustering aids in quantifying information from Kratky and generating shape-descriptive features. SAXS Assistant accelerates SAXS data analysis through enforced quality control, ML-ready outputs, and flags for low-confidence results. In addition to providing the ability to analyze large datasets at high-throughput, this tool is versatile and may serve researchers in both biological and synthetic polymer research fields.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"27 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

A Multimodal Glimpse into the Amyloid Precursor Protein Intracellular Domain Ensembles. 淀粉样前体蛋白胞内结构域集成的多模态一瞥。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-09-23 DOI: 10.1016/j.bpj.2025.09.033

Veronica Isabel Dodero

引用次数: 0

Dynamic Microtubules as Sensors in Animal Cells. 动态微管作为动物细胞的传感器。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-09-23 DOI: 10.1016/j.bpj.2025.09.032

Timothy J Mitchison

{"title":"Dynamic Microtubules as Sensors in Animal Cells.","authors":"Timothy J Mitchison","doi":"10.1016/j.bpj.2025.09.032","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.032","url":null,"abstract":"Microtubules physically organize eukaryotic cells by serving as structural elements and polarized transport tracks. This article advances the hypothesis that dynamic microtubules also serve as sensors of cell shape and cytoplasmic state, building on ideas proposed for higher plant cells1. Microtubule polymerization dynamics and lattice structure are sensitive to mechanical, chemical and signaling inputs which alter the balance between microtubules and soluble tubulin and regulate MAP binding affinity. These changes are detected by transducers which include the GTP exchange factor GEF-H1 (ARHGEF2) and MARK family kinases. The resulting signals regulate cytoplasmic behavior, gene expression and tissue physiology. The microtubule destabilizing drugs colchicine and plinabulin may mimic sensing of pathophysiological cues by microtubules, leading to activation gene expression programs that promote cell survival, growth and repair which account for the therapeutic actions of the drugs. In tissue cells with stable morphologies, the sensory functions of microtubules may be as or more important than their architectural functions. This re-framing of microtubule biology suggests new directions for mechanistic inquiry and drug discovery.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"17 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145133936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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