Biophysical journal最新文献

{"title":"Membrane fusion and budding.","authors":"Arun Anantharam, Michelle K Knowles, Ling-Gang Wu","doi":"10.1016/j.bpj.2025.05.002","DOIUrl":"10.1016/j.bpj.2025.05.002","url":null,"abstract":"","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"E1-E4"},"PeriodicalIF":3.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vesicle docking and fusion pore modulation by the neuronal calcium sensor Synaptotagmin-1.","authors":"Maria Tsemperouli, Sudheer Kumar Cheppali, Felix Rivera-Molina, David Chetrit, Ane Landajuela, Derek Toomre, Erdem Karatekin","doi":"10.1016/j.bpj.2025.02.013","DOIUrl":"10.1016/j.bpj.2025.02.013","url":null,"abstract":"","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"1878"},"PeriodicalIF":3.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple structural states in an intrinsically disordered protein, SNAP-25, using circular dichroism.","authors":"Jarom S Sumsion, Samuel W Shumway, Tanner M Blocker, Thomas D Weed, Tasha M Chambers, Ryan J Poland, Dixon J Woodbury","doi":"10.1016/j.bpj.2025.02.003","DOIUrl":"10.1016/j.bpj.2025.02.003","url":null,"abstract":"<p><p>SNAP-25, together with other SNARE proteins, drives fusion of synaptic vesicles with the nerve cell membrane, leading to neurotransmitter release. It is unique in contributing two α helices to the four-helix bundle known as the SNARE complex. Complex formation drives fusion as these proteins transform from a disordered to ordered (coiled-coil) state. SNAP-25 has two isoforms, -25A and -25B, but little is known of any structural differences, nor are there extensive reports of the structures of its two helical domains, SN1 and SN2. Thus, the benefit of having two distinct isoforms of SNAP-25, each with two distinct domains, is unknown. Here, we use circular dichroism spectroscopy and mass spectrometry to further characterize the secondary structure of SNAP-25A, SNAP-25B, SN1, SN2, and a cysteine-free version of SNAP-25A. We demonstrate that these proteins undergo structural transitions, with changing fractions of α helix, β sheet, and random coil. These different structures can be induced by varying the environmental conditions of ionic strength, pH, temperature, or redox state. We use triangle plots to directly display the change in ternary composition following changes in these four parameters. We report that SNAP-25A and SNAP-25B make distinctly different structural changes. We show that the secondary structure of SN1 is more variable than SN2. These data add to the ongoing literature characterizing SNAP-25 as an intrinsically disordered protein that is sensitive to environmental conditions in neuronal cells and may function as a redox sensor to modulate neurotransmitter release.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"1828-1842"},"PeriodicalIF":3.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Rab3 GTPase cycle modulates cardiomyocyte exocytosis and atrial natriuretic peptide release.","authors":"Kobina Essandoh, Arasakumar Subramani, Sribharat Koripella, Matthew J Brody","doi":"10.1016/j.bpj.2025.03.013","DOIUrl":"10.1016/j.bpj.2025.03.013","url":null,"abstract":"<p><p>Natriuretic peptides are produced predominantly by atrial cardiomyocytes in response to cardiovascular stress and attenuate cardiac maladaptation by reducing blood pressure, blood volume, and cardiac workload primarily through activation of natriuretic peptide receptors in the kidney and vasculature. However, mechanisms underlying cardiomyocyte exocytosis and natriuretic peptide secretion remain poorly defined. Manipulation of Rab3a GTPase activity by Rab3gap1 was recently found to modulate atrial natriuretic peptide (ANP) release by cardiomyocytes. Here, we examined upstream signaling mechanisms and the role of the Rab3a GTPase cycle in exocytosis and ANP secretion by cardiomyocytes. Pharmacological inhibition of the heterotrimeric G protein subunit G⍺q suppressed ANP secretion at baseline and prevented GTP loading of Rab3a and ANP release in neonatal rat cardiomyocytes in response to phenylephrine (PE). Similar to agonist-induced activation of ANP secretion, genetic overexpression of a constitutively active, GTP-loaded Rab3a mutant (Q81L) in neonatal rat cardiomyocytes resulted in enhanced intracellular distribution of Rab3a at endomembranes peripheral to the Golgi and promotion of ANP release, indicating that enhancement of Rab3a activity is sufficient to elicit ANP secretion by cardiomyocytes. Collectively, these data indicate G⍺q signaling downstream of receptor activation and Rab3a-regulated secretory pathway activity and exocytosis facilitate ANP release by cardiomyocytes that could potentially be harnessed to antagonize hypertension and adverse cardiac remodeling in cardiovascular disease.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"1856-1866"},"PeriodicalIF":3.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2Danalysis: A toolbox for analysis of lipid membranes and biopolymers in two-dimensional space.","authors":"Ricardo X Ramirez, Antonio M Bosch, Rubén Pérez, Horacio V Guzman, Viviana Monje","doi":"10.1016/j.bpj.2025.05.026","DOIUrl":"10.1016/j.bpj.2025.05.026","url":null,"abstract":"<p><p>Molecular simulations expand our ability to learn about the interplay of biomolecules. Biological membranes, composed of diverse lipids with varying physicochemical properties, are highly dynamic environments involved in cellular functions. Proteins, nucleic acids, glycans, and biocompatible polymers are the machinery of cellular processes both in the cytosol and at the lipid membrane interface. Lipid species directly modulate membrane properties, and affect the interaction and function of other biomolecules. Natural molecular diffusion results in changes of local lipid distribution, affecting the membrane properties. Projecting biophysical, structural membrane and biopolymer properties to a two-dimensional plane can be beneficial to quantify molecular signatures in a reduced dimensional space to identify relevant interactions at the interface of interest, i.e., the membrane surface or biopolymer-surface interface. Here, we present a toolbox designed to project membrane and biopolymer properties to a two-dimensional plane to characterize patterns of interaction and spatial correlations between lipid-lipid and lipid-biopolymer interfaces. The toolbox contains two hubs implemented using MDAKits architecture, one for membranes and one for biopolymers, that can be used independently or together. Three case studies demonstrate the versatility of the toolbox with detailed tutorials in GitHub. The toolbox and tutorials will be periodically updated with other functionalities and resolutions to expand our understanding of the structure-function relationship of biomolecules in two dimensions. VIDEO ABSTRACT.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224187","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}

{"title":"Extending MMPBSA for membrane proteins: Addressing P2Y12R conformational changes upon ligand binding.","authors":"Cizhang Zhao,Tianhong Wang,Ray Luo","doi":"10.1016/j.bpj.2025.05.023","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.05.023","url":null,"abstract":"Membrane proteins play crucial roles in biological signaling and represent key targets in drug discovery, garnering significant experimental and computational attention. Recent advances in computational screening techniques have enabled the development of more accurate and efficient binding affinity calculation methods. Among these, the Molecular Mechanics Poisson Boltzmann Surface Area (MMPBSA) method has gained widespread adoption in large-scale simulations due to its computational efficiency. However, its application to membrane protein-ligand systems remains less developed compared to globular protein systems, primarily due to the additional complexity introduced by the membrane environment. In this study, we present enhanced capabilities in Amber that provide flexible and automatic options for calculating membrane placement parameters. Furthermore, we present the first application of ensemble simulations, combined with a multi-trajectory approach and entropy corrections, to enhance MMPBSA calculations for membrane protein systems. This novel methodology is particularly advantageous for systems exhibiting large ligand-induced conformational changes, significantly improving accuracy and sampling depth compared to traditional single-trajectory methods. We validate our approach using the human purinergic platelet receptor P2Y12R as a model system, chosen for its well-documented agonist-induced conformational changes and extensive experimental data, making it an ideal candidate for evaluating our enhanced simulation protocol.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"34 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136821","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}

{"title":"Syntaxin 1A transmembrane domain palmitoylation induces a fusogenic conformation.","authors":"Dong An, Satyan Sharma, Manfred Lindau","doi":"10.1016/j.bpj.2025.05.022","DOIUrl":"10.1016/j.bpj.2025.05.022","url":null,"abstract":"<p><p>Neurotransmitter release is triggered by the fusion of synaptic vesicles with the plasma membrane, orchestrated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins synaptobrevin 2 (Syb2), syntaxin 1A (Stx1A), and SNAP25. Recent experimental studies showed that Stx1A palmitoylation of C271/C272 promotes spontaneous neurotransmitter release. However, the mechanistic role of SNARE transmembrane domain (TMD) palmitoylation in membrane fusion remains unclear. To investigate the structural and functional implications of TMD palmitoylation, we employed coarse-grained molecular-dynamics simulations with the MARTINI force field. In simulations of individual SNAREs and of SNAP25/Stx1A (t-SNARE) complexes in a membrane, the palmitoyl chains of Syb2 and Stx1A localize to the membrane midplane, with Stx1A palmitoyl chains bending toward the extracellular leaflet. Nonpalmitoylated Stx1A assumed a conformation where the SNARE domain was lying flat, adhering to the intracellular surface of the membrane. Stx1A dual palmitoylation induced dramatic changes, reducing the tilt of its TMD and stabilizing a more upright conformation of its SNARE domain. This conformation resembles the Stx1A conformation in a t-SNARE complex, providing a potential mechanistic explanation of how Stx1A TMD palmitoylation facilitates early steps in SNARE complex formation and thus promotes spontaneous release. In simulations of the late steps of layers 5-8 SNARE complex zippering in a system of 4 SNARE complexes bridging a 10-nm nanodisc and a planar membrane, fusion pores (FPs) spontaneously opened after a few hundred nanoseconds, preceded by distal-leaflet lipid transfer and followed by FP flickering conductance before FP closure. At this stage, Stx1A TMD palmitoylation delayed lipid transfer and FP formation and decreased FP flicker-open times, whereas the palmitoylation of Syb2 did not affect fusion-pore dynamics. These findings suggest that, after facilitation of priming before FP opening, Stx1A TMD palmitoylation directly affects FP dynamics. These results highlight the essential role of SNARE TMD palmitoylation at multiple stages of neurotransmitter release.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135999","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}

{"title":"Pairwise Encounters Boost Bacterial Motion by Transient Velocity Spikes.","authors":"Pu Feng,Chen Gui,Gancheng Wang,Lingling Wang,Jinglei Hu,Xiangjun Gong,Guangzhao Zhang","doi":"10.1016/j.bpj.2025.05.021","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.05.021","url":null,"abstract":"For swimming bacteria near surfaces, pairwise encounters inevitably occur and impact their social behavior. However, we know little about how the encounter events influence bacterial dynamics due to the limitations in tracking interplaying bacteria in 3D. Herein, we elucidated the motions of encountering E. coli using a combination of 3D holographic tracking experiments and hydrodynamic simulations. We find encounters with other cells induce transient yet remarkable fluctuations in the swimming speed and angle of E. coli, concurrently diminishing their temporal correlations, in contrast to solitary cells. Notably, bacteria approaching each other in a face-to-face fashion both accelerate, whereas they both decelerate during pursuits. Generally, the motion of a pair of smooth-swimming E. coli is dictated by the relative angle, velocity, and intercellular distance, as validated by hydrodynamic simulations. The presence of the surface mitigates the velocity spikes during the encounter process. Additionally, the encounter process influences the timing of tumbles, i.e., tumble tends to occur before the two bacteria get in close proximity. Despite the impact of one encounter being transient, we reveal that smooth-swimming E. coli gains propulsion advantage from the encounter, thus providing insights into bacterial physiology and guidance for designing active microdevices.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"25 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122192","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}

{"title":"Extrinsic heterogeneity: Collectivity in isotropic conformational fluctuations of chromosomes.","authors":"Takuya Nara,Haruko Takahashi,Akinori Awazu,Yutaka Kikuchi","doi":"10.1016/j.bpj.2025.05.020","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.05.020","url":null,"abstract":"Eukaryotic interphase chromosomes maintain a three-dimensional conformation within the nucleus and undergo fluctuations. However, the analysis of chromosome conformational fluctuations has been mainly limited to chromosome conformation capture data that record the contact frequencies between chromosomal regions. Herein, we investigated chromosome fluctuations as polymers based on experimental data from sequential fluorescence in situ hybridization (seqFISH)+ using a multiomics methodology. To describe the principal modes of chromosome fluctuations, we applied principal component analysis to the three-dimensional conformation information of single chromosomes in 446 mouse embryonic stem cells (mESCs) obtained from seqFISH+ data analysis for spatial genomics and signals of nuclear factors (histone marks, repeat DNAs, and proteins in interchromosomal nuclear compartments). We found that chromosome fluctuations exhibit both isotropic and anisotropic modes. The isotropic conformational fluctuations of all chromosome types tended to synchronize each other, reflecting extrinsic heterogeneity in chromosome conformation that is independent of the cell cycle. In contrast, anisotropic conformational fluctuations, occurring in a spindle-like shape, were associated with the interactions between repeat DNAs and nuclear factors. These results highlight the importance of dissecting cell cycle-independent nuclear organization based on the conformational folding of chromosomes and the interactions between genomic regions and nuclear factors.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"2 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144122187","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}

{"title":"Thermodynamics of Arginine Interactions with Organic Phosphates.","authors":"Jiyeon Min,Madolyn Britt,Bernard R Brooks,Sergei Sukharev,Jeffery B Klauda","doi":"10.1016/j.bpj.2025.05.019","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.05.019","url":null,"abstract":"The thermodynamics of arginine-phosphate binding is key to cellular signaling, protein-nucleic acid interactions, and membrane protein dynamics. In biomolecules, monoester phosphates are typically employed as strong electrostatic anchors strategically placed in switch domains to mediate specific interactions. In the diester configuration, phosphate groups act as ubiquitous connectors in all nucleic acids and polar lipids, while also engaging in less specific but multiple electrostatic interactions. Here, we employ isothermal titration calorimetry (ITC) and a set of small-molecule models and peptides to benchmark the ability of the CHARMM force field to accurately reproduce these interactions. We observe good agreement between ITC and computational results for methylguanidinium (MGUA) with glycerol and glucose phosphates (MGUA-Gly3P, MGUA-Glu6P), and for arginine-glycine-arginine peptide with inositol triphosphate (RGR-IP3) systems, with experimental binding energies of -3.30 ± 0.30, -3.89 ± 0.30, and -8.96 ± 0.17 kcal/mol, compared to computational values of -4.08 ± 0.00, -4.20 ± 0.00, and -9.17 ± 0.20 kcal/mol, respectively. However, the experimental binding energy of -2.24 ± 0.71 kcal/mol between MGUA and dimethylphosphate (DMP) in a diester configuration was significantly underestimated in CHARMM computations (-0.51 ± 0.01 kcal/mol). The force field was, therefore, refined by reducing the Lennard-Jones Rmin parameter from 3.55 to 3.405 Å for a specific interaction involving nitrogen and oxygen atoms in MGUA-DMP. Our study brings another experimental means for fine-tuning force field parameters for the phosphates in two distinct configurations and enhances the accuracy of modeling nucleic acids, lipids, and membrane proteins.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"45 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114277","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}