Biochimica et biophysica acta. General subjects最新文献

{"title":"SLAMF9 aggravates myocardial ischemia reperfusion injury through activating the hippo-yap pathway","authors":"Tingting Liu ,&nbsp;Xiuli Guo ,&nbsp;Yanhua Fu ,&nbsp;Weili Zhang","doi":"10.1016/j.bbagen.2025.130821","DOIUrl":"10.1016/j.bbagen.2025.130821","url":null,"abstract":"<div><h3>Background</h3><div>The objective was to investigate the impact of signaling lymphocyte activation molecule family member 9 (SLAMF9) on myocardial infarction (MI) and its mechanisms.</div></div><div><h3>Methods</h3><div>SLAMF9 expression in MI rats was firstly measured. SLAMF9 effect on cardiac functions, myocardial fibrosis, cardiomyocyte hypertrophy, cardiomyocyte apoptosis and inflammation in MI rats was explored using echocardiography, HE staining, masson staining, wheat germ agglutinin staining, western blot, TUNEL staining and qRT-PCR. Meanwhile, SLAMF9 effect on the viability, apoptosis, and inflammation in H9C2 cells was investigated by CCK-8 assay, TUNEL staining and western blot. Moreover, the potential mechanisms of SLAMF9 were investigated using western blot, ELISA and TUNEL staining after different treatment.</div></div><div><h3>Results</h3><div>SLAMF9 expression was upregulated in MI rats. SLAMF9 knockdown ameliorated heart damage, cardiomyocyte apoptosis and inflammatory response in MI rats. Similarly, SLAMF9 silencing in macrophages attenuated the apoptosis and inflammatory response in H/R-induced H9C2 cells. Moreover, SLAMF9 knockdown inhibited Hippo-Yap pathway in MI in vitro and in vivo. Besides, SLAMF9 knockdown in macrophages suppressed the activation of Hippo-Yap pathway in H9C2 cells by inhibiting TNF-α release. Additionally, LATS1 overexpression in H9C2 cells reversed the effect of SLAMF9 silencing on the apoptosis and inflammatory response in H/R-induced H9C2 cells. Meanwhile, PY-60 treatment in H9C2 cells reversed the effect of SLAMF9 overexpression on the apoptosis and inflammatory response in H/R-induced H9C2 cells.</div></div><div><h3>Conclusion</h3><div>The absence of SLAMF9 led to a reduction in TNF-α secretion in macrophages, consequently repressing Hippo-Yap pathway in cardiomyocytes, and ultimately ameliorating myocardial damage, cardiomyocyte apoptosis and inflammation in MI.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130821"},"PeriodicalIF":2.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092288","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":"Decoding the calcium signal: Structural insights into CBL-CIPK pathway in plants","authors":"Subhash Chandra Bihani ,&nbsp;Tarushi ,&nbsp;Ashish Kumar Srivastava","doi":"10.1016/j.bbagen.2025.130819","DOIUrl":"10.1016/j.bbagen.2025.130819","url":null,"abstract":"<div><div>Calcium (Ca²⁺) signaling in plants is a major pathway in transducing diverse environmental stimuli. Calcineurin B-like proteins (CBLs) are one of the unique groups of Ca²⁺ sensors that transduce the Ca²⁺ signals by interacting with plant-specific protein kinases known as CBL-interacting protein kinases (CIPKs). In recent years, structure-function studies have provided key insights into the molecular basis of CBL-CIPK signaling and their interactions with the target proteins. The crystal structures of CBL2 and CBL4 have elucidated the architecture of non-canonical EF hands and provided the rationale for Ca²⁺ binding by CBLs. The molecular basis of interaction of the regulatory domain of CIPKs with CBLs has been established, providing rationale for CBL-mediated activation of CIPKs. The molecular mechanism of fine regulation of CIPK activity under non-stressed conditions and full activation under stressed conditions has been established using crystal structures of CIPK23 and CIPK24. Recently, high-resolution CryoEM structures of Arabidopsis and rice SOS1 led to a comprehensive understanding of its regulation and ion transport mechanism. In this review, major advances in understanding the structural basis of Ca²⁺ sensing by CBLs, molecular determinants of CIPK activation, and subsequent phosphorylation of target proteins are discussed. Remaining questions that need to be answered for a holistic understanding of the CBL-CIPK network are also discussed.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130819"},"PeriodicalIF":2.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075771","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":"Cyanobacterial KdpD modulates in vivo and in vitro activities of a membrane-anchored histidine kinase","authors":"Anand Ballal ,&nbsp;Shree Kumar Apte","doi":"10.1016/j.bbagen.2025.130817","DOIUrl":"10.1016/j.bbagen.2025.130817","url":null,"abstract":"<div><div>The prokaryotic KdpATPAse complex, encoded by the <em>kdpABC</em> operon, is an inducible, high-affinity K⁺ transporter. In <em>E. coli</em>, the operon is transcriptionally regulated by a two-component sensor-kinase response-regulator system, constituted by the KdpD and KdpE proteins. In contrast, cyanobacteria exhibit a truncated <em>kdpD</em> gene that encodes a KdpD homolog that is similar to the N-terminal domain (NTD) of <em>E. coli</em> KdpD, but lacks the transmitter, histidine kinase-containing, C-terminal domain (CTD). Here we show that the cyanobacterium <em>Anabaena</em> sp. strain L-31 constitutively transcribes the short <em>kdpD</em> gene, but synthesizes KdpATPase only during potassium starvation. However, unlike <em>E. coli</em>., expression of the <em>kdpD</em> gene remains unaffected by K⁺ limitation in <em>Anabaena</em>. To gain insight into the possible role of <em>Anabaena</em> KdpD, the chimeric Anacoli KdpD protein, wherein the NTD of <em>E. coli</em> KdpD was replaced with <em>Anabaena</em> KdpD, was functionally analyzed. Detailed investigation has revealed that the Anacoli KdpD (a) responds to a much lower threshold of external K⁺ than the <em>E. coli</em> KdpD (b) exhibits much reduced ability to induce <em>kdp</em> in response to ionic osmolytes than <em>E. coli</em> KdpD, and is therefore unable to sustain optimal growth in the presence of these osmolytes and (c) displays higher in vitro phosphatase activity than the wild type <em>E. coli</em> KdpD. Thus, <em>Anabaena</em> KdpD modulates properties of <em>E. coli</em> KdpD-CTD in a manner that is quite distinct from the <em>E. coli</em> KdpD-NTD. Based on these evidences, a model for <em>kdp</em> regulation by the short KdpD is proposed.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130817"},"PeriodicalIF":2.8,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970216","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":"There is more to scanning than meets the eye: Raster Image Correlation Spectroscopy","authors":"Irene Gialdini ,&nbsp;Jelle Hendrix ,&nbsp;Don C. Lamb","doi":"10.1016/j.bbagen.2025.130818","DOIUrl":"10.1016/j.bbagen.2025.130818","url":null,"abstract":"<div><div>Raster Image Correlation Spectroscopy (RICS) is a confocal image analysis method that can measure the diffusion and interactions of fluorescently labeled molecules in real time in solution and in living cells. RICS is easy to implement on commercial confocal microscopes and allows detailed investigations of complex biological systems and pathways. The method is especially robust for measurements in living cells using commonly used labels such as fluorescent proteins. Moreover, since its invention in 2005, the robustness and applicability of RICS has been significantly increased to allow, e.g., straightforward kinetic analyses, advanced image segmentation, parameter mapping, and multi-species analysis. In this review, we describe the methodological principles of RICS in a manner that is accessible to a broad readership, position RICS in relation to other fluorescence fluctuation techniques, highlight recent methodological advances and present exemplary applications of the method. With this review, we hope to facilitate the implementation of this powerful method into the everyday repertoire of confocal imaging approaches.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130818"},"PeriodicalIF":2.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955920","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":"LACTB promotes cell differentiation and inhibits cell proliferation in colorectal cancer","authors":"Lili Ma ,&nbsp;Guan Huang ,&nbsp;Chun Lin ,&nbsp;Xiaoqing Li ,&nbsp;Chao Liu ,&nbsp;Weiye Huang ,&nbsp;Qingling Zhang ,&nbsp;Yang Luo","doi":"10.1016/j.bbagen.2025.130816","DOIUrl":"10.1016/j.bbagen.2025.130816","url":null,"abstract":"<div><div>This study aims at exploring the role of LACTB on colorectal cancer (CRC) cell differentiation. In this study, 143 colorectal cancer tissue samples were collected for analyzing the correlation between LACTB level and clinical information. Another 24 recent cases and adjacent tissues underwent qPCR, Western blot, and immunohistochemistry (IHC) to detect LACTB expression. The differentiation and proliferation of CRC cells were evaluated by AKP levels, E-cadherin expression, cell viability, colony formation, EdU assay, and cell cycle. Subcutaneous models explored LACTB's pro-differentiation effects. The glandular-like structures of tumor were observed by HE staining, immunofluorescence detection of microvilli proteins, and transmission electron microscopy. Our results showed that LACTB expression in colorectal cancer tissues was lower than that in adjacent normal tissues. Higher LACTB expression was correlated with slower tumor progression, better prognosis and higher differentiation degree. Overexpressing LACTB in CRC cells enhanced differentiation markers level (AKP and E-cadherin), while inhibited cell proliferation and colony formation, induced cell cycle arrest. Conversely, LACTB knockdown had an opposite effect. Subcutaneous xenograft tumor model suggested that LACTB overexpression inhibited tumor growth, induced tissue differentiation and glandular-like structures formation. Collectively, our results show that LACTB overexpression promotes cell differentiation and inhibits cell proliferation in CRC cells, which may serve as a therapy target for CRC.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130816"},"PeriodicalIF":2.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958318","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":"Unraveling architectural RNAs: Structural and functional blueprints of membraneless organelles and strategies for genome-scale identification","authors":"Naoko Fujiwara,&nbsp;Tsuyoshi Ueno,&nbsp;Tomohiro Yamazaki,&nbsp;Tetsuro Hirose","doi":"10.1016/j.bbagen.2025.130815","DOIUrl":"10.1016/j.bbagen.2025.130815","url":null,"abstract":"<div><div>Architectural RNAs (arcRNAs) are long noncoding RNAs that serve as structural scaffolds for membraneless organelles (MLOs), facilitating cellular organization and dynamic responses to stimuli. Acting as blueprints for MLO assembly, arcRNAs recruit specific proteins and nucleic acids to establish and maintain the internal structure of MLOs while coordinating their spatial relationships with other organelles. This organized framework enables precise spatiotemporal regulation, allowing for targeted control of transcription, RNA processing, and cellular responses to stress. Notably, arcRNAs exhibit the “semi-extractable” feature, a property derived from their stable binding to cellular structures, making them partially resistant to conventional RNA extraction methods. This unique feature serves as a useful criterion for identifying novel arcRNAs, providing an opportunity to accelerate research in long noncoding RNAs and deepen our understanding of their functional roles in cellular processes.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 8","pages":"Article 130815"},"PeriodicalIF":2.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973739","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":"Factories without walls: The molecular architecture and functions of non-membrane organelles in small RNA-guided genome protection","authors":"Shinichi Kawaguchi,&nbsp;Wakana Isshiki,&nbsp;Toshie Kai","doi":"10.1016/j.bbagen.2025.130811","DOIUrl":"10.1016/j.bbagen.2025.130811","url":null,"abstract":"<div><div>Non-membrane organelles, Yb body and nuage, play an essential role in piRNA-guided genome defense in <em>Drosophila</em> gonad by mediating piRNA biogenesis and transposon silencing. Yb body, found in somatic follicle cells, is responsible for primary piRNA processing, while nuage, located in germline cells, facilitates the ping-pong cycle to amplify the piRNAs corresponding to both sense and antisense strands of the expressed transposons. These organelles are assembled by liquid-liquid phase separation (LLPS) and protein-protein interactions, integrating RNA helicases (Vasa, Armitage), Tudor domain-containing proteins (Krimper, Tejas, Qin/Kumo), and proteins containing both domains (Yb, SoYb, Spn-E). Within these condensates, we summarize the protein-protein interactions experimentally validated and predicted by AlphaFold3, providing new structural insights into the non-membrane organelle assembly. This review highlights how the dynamic organization of Yb body and nuage enables efficient RNA processing, ensuring transposon suppression and genome stability.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 7","pages":"Article 130811"},"PeriodicalIF":2.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899034","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":"Systemically administered mini α-crystallin peptide delays cataract progression in streptozotocin-induced diabetic rats","authors":"Pandarinath Savitikadi ,&nbsp;Lucky Dash ,&nbsp;Kiran Kumar Angadi,&nbsp;G. Bhanuprakash Reddy,&nbsp;V. Sudhakar Reddy","doi":"10.1016/j.bbagen.2025.130814","DOIUrl":"10.1016/j.bbagen.2025.130814","url":null,"abstract":"<div><div>α-Crystallin in the mammalian eye lens composed of αA-Crystallin (αAC) and αB-Crystallin (αBC) subunits present in a 3:1 ratio. These proteins exhibit chaperone-like activity, helping to protect cells from various forms of stress. Specific sequences within αAC (⁷⁰KFVIFLDVKHFSPEDLTVK⁸⁸) and αBC (⁷³DRFSVNLDVKHFSPEELKVK⁹²) have been shown to possess effective chaperone and anti-apoptotic properties. However, their protective effects in diabetic cataract (DC) have not been explored. The current study explored the protective effects of systemically administered mini-αA and αBC peptides, both individually and in combination (3:1 ratio) against streptozotocin (STZ)-induced DC in rats. Hyperglycemia was induced in Sprague-Dawley rats through intraperitoneal (I.P.) injection of STZ, while control rats received PBS. Starting from the onset of cataract development, a group of diabetic rats was treated with mini-αA, or mini-αB, or their combination for four months via IP administration. Cataract progression and maturation were monitored using a slit lamp biomicroscope. To understand the underlying biochemical and molecular processes, we assessed changes in protein content, protein insolubilization, oxidative stress, endoplasmic reticulum (ER) stress, apoptotic cell death, and caspase-3 activity. Although the mini peptides did not prevent STZ-induced hyperglycemia, they delayed cataract progression in diabetic rats. Furthermore, mini peptides reduced protein aggregation and insolubilization, alleviated oxidative and ER stress, and mitigated hyperglycemia-induced apoptosis by lowering caspase-3 activity and Bax levels. This study demonstrates that systemic administration of mini α-crystallin peptides can delay DC progression by mitigating protein aggregation, oxidative stress, ER stress, and apoptosis. These findings suggest potential therapeutic applications for mini α-crystallin peptides in treating DC.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 7","pages":"Article 130814"},"PeriodicalIF":2.8,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901971","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":"27-hydroxycholesterol impairs placental development via p53/p21/Cdk6 pathway: Implications for nutrient transport and cellular senescence","authors":"Zhaoyang Chen ,&nbsp;Xiaxia Cai ,&nbsp;Yuchen Wei ,&nbsp;Xiaoyan Zhao ,&nbsp;Qinyu Dang ,&nbsp;Yandi Zhu ,&nbsp;Ming Gao ,&nbsp;Yulu Zhang ,&nbsp;Yadi Zhang ,&nbsp;Huanling Yu","doi":"10.1016/j.bbagen.2025.130806","DOIUrl":"10.1016/j.bbagen.2025.130806","url":null,"abstract":"<div><div>Aberrant placental development and function contribute to various pregnancy complications. 27-hydroxycholesterol (27-OHC), a recognized mediator linking hypercholesterolemia and metabolic diseases, has an undefined role in placental development. This study investigates the impact of 27-OHC on placental development and its underlying mechanisms, particularly in relation to cellular senescence. Pregnant mice were subcutaneously administered either 27-OHC (27-OHC group) or normal saline (control group) during gestation. Subsequently, placentas underwent spatial transcriptome (ST) sequencing. The levels of genes and proteins related to nutrient transport, cell cycle and senescence associated secretory phenotype were validated. Additionally, BeWo cells were treated with 27-OHC at concentrations of 2.5, 5 and 10 μM during its differentiation and fusion to observe the effects and mechanisms of trophoblast cell senescence. In the 27-OHC group, the labyrinth zone area and combined fetal-placental weight were significantly reduced compared to the control group. ST analysis revealed alterations in placental cell composition and downregulation of nutrient transport processes, alongside pathways linked to senescence, including the p53/p21/Cdk6 pathway, specifically in Syncytiotrophoblast Type I (SynT I) cells. In both mouse placentas and BeWo cells, mRNA and protein levels of p53 and p21 were reduced in the 27-OHC group compared to controls. During late pregnancy, 27-OHC inhibits the physiological senescence of placental syncytiotrophoblasts and may affect nutrient transport within the placenta. The inhibition of the p53/p21/Cdk6 pathway may represent one of the key mechanisms involved.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 7","pages":"Article 130806"},"PeriodicalIF":2.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874906","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":"Probing the relationships between self-assembly and the antimicrobial activity of amyloidogenic peptides: The islet amyloid polypeptide as a case study","authors":"Vy Nguyen ,&nbsp;Mélanie Côté-Cyr ,&nbsp;Arthur Nery Finatto ,&nbsp;Margaryta Babych ,&nbsp;Phuong Trang Nguyen ,&nbsp;Mathew Sebastiao ,&nbsp;Steve Bourgault","doi":"10.1016/j.bbagen.2025.130812","DOIUrl":"10.1016/j.bbagen.2025.130812","url":null,"abstract":"<div><div>Antimicrobial peptides (AMPs) are key components of the innate immune system across diverse organisms. Interestingly, some AMPs can adopt β-sheet secondary structure and self-assemble into amyloid-like fibrils. Recent works have also revealed that amyloidogenic peptides exhibit antimicrobial properties and share a common mechanism of plasma membrane perturbation with AMPs. In this study, we explored the relationships between the antimicrobial activity of amyloidogenic peptides and their self-assembly by using the islet amyloid polypeptide (IAPP) as a model. IAPP is an aggregation-prone 37-residue hormone whose pancreatic deposition and accumulation are associated with type II diabetes. Antimicrobial assays revealed that IAPP monomers and prefibrillar aggregates, including soluble oligomers, inhibit the growth of <em>Escherichia coli</em> and <em>Staphylococcus epidermidis</em>. Additionally, monomeric and prefibrillar proteospecies perturbed anionic lipid vesicles that mimic bacterial plasma membrane and decrease the metabolic activity. In contrast, pre-assembled amyloid fibrils exhibited weak antimicrobial activities and lipid membrane perturbation, although they agglutinated bacteria avidly. By taking advantage of residue-specific substitutions that modulate the aggregation propensity, we observed that derivatives with hindered amyloidogenicity retained antimicrobial activities, while those with accelerated kinetics of amyloid self-assembly had weaker antimicrobial effect. Moreover, by modulating the propensity of IAPP to fold into an α-helix, we observed that amyloid formation is not a prerequisite for the antimicrobial activity, while the destabilization of helical folding reduced IAPP antimicrobial activity. This study provides fundamental mechanistic insights of the modest antimicrobial activity of IAPP and highlights that precaution should be taken before generalizing the antimicrobial potential of self-assembling amyloid polypeptides.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 7","pages":"Article 130812"},"PeriodicalIF":2.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870200","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}