Journal of Membrane Biology最新文献_第3页

Protonation of Key Acidic Residues Reveals Binding Features of PCABs to Gastric H, K-ATPase. 关键酸性残基的质子化揭示了pcab与胃H， k - atp酶的结合特征。

IF 2.6 4区生物学

Journal of Membrane Biology Pub Date : 2026-05-30 DOI: 10.1007/s00232-026-00383-6

Gerardo Zerbetto De Palma, Nicole T Cerf, Mónica R Montes

{"title":"Protonation of Key Acidic Residues Reveals Binding Features of PCABs to Gastric H, K-ATPase.","authors":"Gerardo Zerbetto De Palma, Nicole T Cerf, Mónica R Montes","doi":"10.1007/s00232-026-00383-6","DOIUrl":"10.1007/s00232-026-00383-6","url":null,"abstract":"The group of inhibitors known as Potassium Competitive Acid Blockers (PCABs) has become one of the main topics of current research into reducing gastric H,K-ATPase activity. The design of novel PCABs relies on structure-based drug design strategies that integrate structural data with molecular dynamics simulations. A key aspect in conventional molecular dynamics simulations is the assignment of residue charge states, since the local physicochemical environment influences the pKa of amino acids. This computational work investigates the impact of the protonation state of key residues on the interactions between PCABs and the gastric H,K-ATPase. The study focusses on Glu343, Glu795, and Glu820, from the cation binding cavity, and vonoprazan and tegoprazan; two chemically unrelated PCABs. The results show how protonation states generate changes in interactions, especially with the charged group of inhibitors. Simulations in which Glu343 or Glu795 were protonated showed that the charged secondary amine of vonoprazan could rotate freely, favoring hydrogen bonding with some of the glutamic residues deep within the pocket. In contrast, the positive charge of tegoprazan is located in the benzimidazole ring, a rigid and bulky structure, which moves away from the center of the cavity when Glu343 or Glu795 are protonated. The inspection of the ionization states of amino acids reveals the conformational flexibility of the protonated group of PCABs as pivotal for binding affinity and highlights the importance of considering the protonation state of protein residues before performing any conventional molecular dynamics simulations for drug design.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148102188","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

Electrostatic Interaction as a Key Modulator of Na⁺,K⁺-ATPase Function. 静电相互作用作为Na+，K+- atp酶功能的关键调制器。

IF 2.6 4区生物学

Journal of Membrane Biology Pub Date : 2026-05-26 DOI: 10.1007/s00232-026-00382-7

Shadreen Fairuz, Zhitong Li, Amy Gorman, Flemming Cornelius, Ronald J Clarke

{"title":"Electrostatic Interaction as a Key Modulator of Na+,K+-ATPase Function.","authors":"Shadreen Fairuz, Zhitong Li, Amy Gorman, Flemming Cornelius, Ronald J Clarke","doi":"10.1007/s00232-026-00382-7","DOIUrl":"10.1007/s00232-026-00382-7","url":null,"abstract":"The Na+,K+-ATPase is an integral membrane protein present in all animal plasma membranes. It uses the energy of ATP hydrolysis to pump 3 Na+ ions per ATP hydrolysed from the cell cytoplasm into the extracellular fluid in exchange for 2 K+ ions. The Na+ electrochemical potential gradient it produces is used as an energy source to drive all animal secondary transporters, for example, in nutrient reabsorption in the kidney. In this synthesis of new and previously published results, it is shown that the rate of the mammalian enzyme's rate-determining E2 → E1 conformational change, during which K+ ions are released to the cytoplasm, is strongly dependent on an electrostatic interaction in the E2 state. This electrostatic interaction must be broken to allow the enzyme to convert to the E1 state and allow Na+ pumping. The strength of the interaction depends on ionic strength and, even more strongly, on the concentration of divalent metal ions, i.e., Ca2+ or Mg2+. A likely candidate for the interaction is between the protein's positively-charged lysine-rich N-terminus and the negatively-charged membrane cytoplasmic surface. Comparison of the Ca2+ and Mg2+ dissociation constants measured with the physiological levels of the two ions suggests that Mg2+, but not Ca2+, could play a regulatory role for the Na+,K+-ATPase.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148037229","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

Evolutionary Prevalence of the Electrostatic Switch Mechanism in P-type ATPases. p型atp酶静电开关机制的进化普遍性。

IF 2.6 4区生物学

Journal of Membrane Biology Pub Date : 2026-05-26 DOI: 10.1007/s00232-026-00377-4

Nikita S Badve, Alyssa V Buda, Jonas A Káral, Zhitong Li, Taylah L Percival, Sofia Y Wardman, Sophia G Tran, Simon Y W Ho, Ronald J Clarke

{"title":"Evolutionary Prevalence of the Electrostatic Switch Mechanism in P-type ATPases.","authors":"Nikita S Badve, Alyssa V Buda, Jonas A Káral, Zhitong Li, Taylah L Percival, Sofia Y Wardman, Sophia G Tran, Simon Y W Ho, Ronald J Clarke","doi":"10.1007/s00232-026-00377-4","DOIUrl":"10.1007/s00232-026-00377-4","url":null,"abstract":"P-type ATPases are active transporter enzymes that maintain ion electrochemical gradients for functions such as muscle contraction, kidney function, digestion, and nerve signalling. The dysfunction of these ATPases has been linked to several neurological, cardiovascular, and metabolic disorders. An electrostatic switch mechanism (ESM) has been hypothesised to be involved in the regulation of the sodium-potassium pump (Na+,K+-ATPase) and the gastric proton pump (H+,K+-ATPase). An analysis of primary and tertiary protein structures suggests a potentially higher prevalence of the ESM in human P-type ATPases than previously thought. Evidence for the ESM was found on the N-terminus for the P1B, and P2C subfamilies of P-type ATPases, and on the C-terminus for the P2A and P5 subfamilies. In the case of the P4 family, evidence for the ESM was found on the N-terminus for some subfamilies and on the C-terminus for others. Evidence for the ESM has been identified in P-type ATPase subfamilies distributed in separate lineages of the phylogenetic tree, suggesting that the ESM evolved multiple times independently.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13212812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148037256","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

Fluorescence Lifetime Spectroscopy Reveals Distinct Allosteric Mechanisms of SERCA Inhibitors. 荧光寿命光谱揭示了SERCA抑制剂不同的变构机制。

IF 2.6 4区生物学

Journal of Membrane Biology Pub Date : 2026-05-20 DOI: 10.1007/s00232-026-00380-9

Jaroslava Šeflová, Carlos Cruz-Cortés, Seth L Robia, L Michel Espinoza-Fonseca

{"title":"Fluorescence Lifetime Spectroscopy Reveals Distinct Allosteric Mechanisms of SERCA Inhibitors.","authors":"Jaroslava Šeflová, Carlos Cruz-Cortés, Seth L Robia, L Michel Espinoza-Fonseca","doi":"10.1007/s00232-026-00380-9","DOIUrl":"10.1007/s00232-026-00380-9","url":null,"abstract":"We recently developed a time-correlated single photon counting (TCSPC) spectroscopy approach to investigate the activation mechanisms of the calcium pump SERCA (sarcoplasmic reticulum Ca2+-ATPase). Here, we apply this approach to characterize the effects of two chemically distinct SERCA inhibitors, thapsigargin (TG) and cyclopiazonic acid (CPA), and to determine how they differentially modulate SERCA conformational dynamics. Although TG and CPA appear to stabilize similar SERCA states in structural studies, TCSPC reveals fundamentally distinct mechanisms of inhibition. TG stabilizes an inactive conformation that prevents Ca2+- and ATP-dependent transitions, effectively trapping SERCA in a nonproductive 'dead-end' state. In contrast, CPA attenuates, rather than abolishes, Ca2+- and nucleotide-dependent structural transitions, producing graded, concentration-dependent effects that reduce the population of the closed, activation-associated state. Notably, CPA decreases apparent Ca2+ affinity only in the presence of a non-hydrolyzable ATP analog, consistent with an ATP-dependent, allosteric mechanism that redistributes conformational populations rather than directly occluding Ca2+ binding sites. These findings demonstrate that TCSPC resolves mechanistic differences between inhibitors that appear structurally similar and provide a framework for understanding how distinct allosteric ligands modulate SERCA function.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13190474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147976908","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

IUPAB Focused-Meeting on P-Type ATPases: 17th International Conference on P-type ATPases in Health and Disease. IUPAB聚焦于p型atp酶会议：第17届健康与疾病p型atp酶国际会议。

IF 2.6 4区生物学

Journal of Membrane Biology Pub Date : 2026-05-20 DOI: 10.1007/s00232-026-00378-3

Ronald J Clarke

引用次数: 0

Structure-Function Insights into Anionic and Cationic Undecapeptides: A Combined Modeling and Antibacterial Study. 阴离子和阳离子非肽的结构-功能洞察：一种联合建模和抗菌研究。

IF 2.6 4区生物学

Journal of Membrane Biology Pub Date : 2026-05-20 DOI: 10.1007/s00232-026-00379-2

Thang Nguyen Quoc, Hai Bui Thi Phuong, Duc Nguyen Van, Duc Nguyen Minh, Hoang Vu Dinh, Tung Truong Thanh, Huy Luong Xuan

{"title":"Structure-Function Insights into Anionic and Cationic Undecapeptides: A Combined Modeling and Antibacterial Study.","authors":"Thang Nguyen Quoc, Hai Bui Thi Phuong, Duc Nguyen Van, Duc Nguyen Minh, Hoang Vu Dinh, Tung Truong Thanh, Huy Luong Xuan","doi":"10.1007/s00232-026-00379-2","DOIUrl":"10.1007/s00232-026-00379-2","url":null,"abstract":"Antimicrobial peptides (AMPs) represent a promising class of alternatives to conventional antibiotics. In this study, we compared the structural and functional properties of three synthetic undecapeptides: the anionic Cn-AMP2 and its N-terminally acetylated derivative (Ac-CnAMP2), versus the cationic α-helical peptide BP52. While BP52 exhibited strong antibacterial activity against both Gram-positive and Gram-negative bacteria, Cn-AMP2 and Ac-CnAMP2 showed no measurable antibacterial effects up to 128µM. Hemolysis assays revealed that BP52 caused mild to moderate lysis of red blood cells, whereas the anionic peptides were non-hemolytic. Molecular dynamics simulations confirmed the enhanced membrane insertion, clustering behavior, and bilayer disruption induced by BP52, in contrast to the limited interaction profiles of Cn-AMP2. These findings underscore the importance of positive charge, helical conformation, and amphipathic topology in driving membrane action and offer insights for designing optimized AMP-based therapeutics.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147976917","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

Deciphering Membrane Pore Formation Mechanisms of Plasmodium falciparum Perforin-Like Protein 1 (PfPLP1). 恶性疟原虫穿孔素样蛋白1 （PfPLP1）膜孔形成机制的解读。

IF 2.6 4区生物学

Journal of Membrane Biology Pub Date : 2026-05-09 DOI: 10.1007/s00232-026-00376-5

Sanket B Patil, Subrata Dasgupta, Prasenjit Bhaumik

{"title":"Deciphering Membrane Pore Formation Mechanisms of Plasmodium falciparum Perforin-Like Protein 1 (PfPLP1).","authors":"Sanket B Patil, Subrata Dasgupta, Prasenjit Bhaumik","doi":"10.1007/s00232-026-00376-5","DOIUrl":"10.1007/s00232-026-00376-5","url":null,"abstract":"Membrane Attack Complex/Perforin (MACPF) domain proteins are β-pore forming toxins (β-PFTs) involved in the pathogenesis of various organisms. Among them, Perforin-like proteins (PLPs), produced by Plasmodium species, play essential roles in parasite invasion and egress. Due to increasing drug resistance in Plasmodium, PLPs represent promising but underexplored therapeutic targets, largely due to the lack of structural and mechanistic data. This study investigates the binding and pore formation mechanism of the Plasmodium falciparum PLP1 (PfPLP1), which is expressed during the human life cycle of the parasite. We modeled PfPLP1 structure and performed both all-atom and coarse-grained molecular dynamics simulations in soluble and membrane-associated states. PfPLP1 comprises two domains, a canonical MACPF domain and a β-pleated sheet domain- apicomplexan perforin β-domain (APCβ). Initial membrane binding is mediated by cationic residues at the base of the APCβ domain, which interact with the polar headgroups of the lipids from the host cell membrane. We analyzed the membrane-inserted tetrameric form where water molecules were observed to penetrate between the tetramer and the lipid bilayer, initiating pore opening. During this process, lipids reorganize into a toroidal edge to shield their hydrophobic tails, while water mixes with lipid headgroups in a disordered, heterogeneous fashion. Larger oligomeric assemblies show lateral displacement of lipids and a clear tendency to form pore-like structures. This study provides molecular insights into PfPLP1's membrane binding and pore-forming behavior in both monomeric and oligomeric forms. The outcome of this study would be applicable in understanding pore formation mechanism in other PLPs and similar toxins.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864758","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

Molecular Partners of Voltage-Gated Calcium Channel β and α₂δ Auxiliary Subunits: Roles in Channel Complex Regulation and Beyond. 电压门控钙通道β和α2δ辅助亚基的分子伙伴：在通道复合体调控及其他方面的作用。

IF 2.6 4区生物学

Journal of Membrane Biology Pub Date : 2026-03-16 DOI: 10.1007/s00232-026-00371-w

Alejandra Corzo-López, Margarita Leyva-Leyva, Ricardo González-Ramírez, Alejandro Sandoval, Ricardo Felix

{"title":"Molecular Partners of Voltage-Gated Calcium Channel β and α2δ Auxiliary Subunits: Roles in Channel Complex Regulation and Beyond.","authors":"Alejandra Corzo-López, Margarita Leyva-Leyva, Ricardo González-Ramírez, Alejandro Sandoval, Ricardo Felix","doi":"10.1007/s00232-026-00371-w","DOIUrl":"10.1007/s00232-026-00371-w","url":null,"abstract":"Research on the auxiliary subunits β (CaVβ) and α2δ (CaVα2δ) of voltage-gated calcium channels has gained increasing interest as novel and unexpected functional interactions for these proteins are discovered. Beyond their classic role as regulators of the channel complex, these subunits participate in the spatiotemporal fine-tuning of the channels and in diverse cellular processes. Currently, multiple studies are investigating the interactions between CaVβ and CaVα2δ with other proteins outside the channel complex, and how these associations affect relevant cellular functions such as cell growth, differentiation, and gene expression beyond their effects on channel activity. The auxiliary subunits have also been observed to associate with components involved in calcium channel biogenesis, a process independent of the direct modulation of channel activity. Furthermore, their involvement in the intracellular transport of other channels and receptors, as well as in nuclear signaling, has been demonstrated. The expression of different variants or isoforms may fulfill specific functions in diverse tissues and developmental stages, even outside the channel complex. Undoubtedly, the study of these proteins as scaffolding or regulatory molecules for other proteins has significantly enriched our understanding of their influence on cell signaling and excitability.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12992490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469994","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

Deciphering the Influence of Side Chains of Short Cationic Hydrophobic Peptides on Macroscopic and Molecular Properties of Mixed Lipid Bilayers. 解析短阳离子疏水肽侧链对混合脂质双层宏观和分子性质的影响。

IF 2.6 4区生物学

Journal of Membrane Biology Pub Date : 2026-03-11 DOI: 10.1007/s00232-026-00373-8

Lea Pašalić, Andreja Jakas, Ana Čikoš, Barbara Pem, Danijela Bakarić

{"title":"Deciphering the Influence of Side Chains of Short Cationic Hydrophobic Peptides on Macroscopic and Molecular Properties of Mixed Lipid Bilayers.","authors":"Lea Pašalić, Andreja Jakas, Ana Čikoš, Barbara Pem, Danijela Bakarić","doi":"10.1007/s00232-026-00373-8","DOIUrl":"10.1007/s00232-026-00373-8","url":null,"abstract":"Cell-penetrating peptides (CPPs) are increasingly used for delivering cargo into cells, but the mechanisms of their membrane crossing remain poorly understood, even for shorter cationic hydrophobic peptides. This study explores how cationic hydrophobic peptides with various combinations of cationic (K and R) and hydrophobic (W and I) amino acids interact with lipid bilayers made of 90% neutral lipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (PC) and 10% anionic lipids (either 1,2-dipalmitoyl-sn-glycero-3-phosphatidylglycerol (PG) or 1,2-dipalmitoyl-sn-glycero-3-phosphoserine (PS)). Specifically, it was found that changing the hydrophobic segment from W to I significantly influences turbidity during the pretransition for the PC/PG mixture. Conversely, in the PC/PS mixture, the interaction with I-peptides causes changes in turbidity during the main phase transition, regardless of whether the cationic segment is R or K. Molecular features analyzed through FTIR spectroscopy revealed significant differences in the vibrations of methylene groups within hydrocarbon chains. In the presence of I-peptides, regardless of whether they are R or K derivatives, a notably higher number of kink conformers were observed compared to W-peptides. Although W-peptides tend to form aggregates due to the insertion of their hydrophobic segments into the lipid bilayer, they appear to maintain the membrane's integrity and the organization of lipids. In contrast, the branched side chains of the I-segment induce out-of-plane movements in the hydrocarbon chains. As the initial interaction between the peptide and the lipid membrane is crucial for its translocation, these findings provide insights into the molecular events occurring before translocation and emphasize the specifics that make it unique to CPPs.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147437032","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

Mechanistic Insights into Human Defensin Antimicrobial Activity from Membrane Simulations. 从膜模拟研究人类防御素抗菌活性的机理。

IF 2.6 4区生物学

Journal of Membrane Biology Pub Date : 2026-03-04 DOI: 10.1007/s00232-026-00372-9

Anna K Manukyan

{"title":"Mechanistic Insights into Human Defensin Antimicrobial Activity from Membrane Simulations.","authors":"Anna K Manukyan","doi":"10.1007/s00232-026-00372-9","DOIUrl":"10.1007/s00232-026-00372-9","url":null,"abstract":"Defensins function as critical effectors of innate immunity, displaying broad-spectrum antimicrobial activity against bacteria, fungi, and viruses. While experimental studies have extensively characterized these peptides, the molecular mechanisms governing their membrane interactions remain poorly understood. This investigation employed comprehensive molecular dynamics simulations to analyze six defensins (human and rabbit α-defensins HNP1, HNP3, rabbit NP4 and human β-defensins HBD1, HBD2, HBD3) using the IMM1 implicit membrane model for studying interactions with anionic bacterial membranes. Both monomeric and dimeric forms were examined to elucidate oligomerization effects on membrane binding and penetration mechanisms. Transfer energy calculations revealed distinct binding patterns and orientations among different defensin subtypes, with β-defensins demonstrating superior membrane affinity compared to α-defensins. HBD3 exhibited the most favorable membrane interactions, correlating with its exceptional antimicrobial potency. Binding orientation analysis demonstrated that defensins adopt specific membrane-bound configurations that optimize electrostatic interactions with anionic membrane surfaces while strategically positioning hydrophobic regions for effective membrane insertion. These findings provide molecular level insights into defensin selectivity mechanisms for bacterial membranes and establish a foundation for defensin-based therapeutic development. The results validate that computational approaches effectively complement experimental studies in elucidating complex antimicrobial peptide mechanisms. This modeling framework supports rational design of next generation defensin therapeutics with optimized antimicrobial activity and pathogen selectivity.","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147357136","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