{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:04:58Z","timestamp":1785769498099,"version":"3.56.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Membrane Biol"],"published-print":{"date-parts":[[2025,8]]},"DOI":"10.1007\/s00232-025-00349-0","type":"journal-article","created":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T20:30:08Z","timestamp":1749414608000},"page":"341-352","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Oxysterols Outcompete Cholesterol Binding to the Membrane-Inserted Cytolysin A Pore Complex"],"prefix":"10.1007","volume":"258","author":[{"given":"Samlesh","family":"Choudhury","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bharath","family":"Desikan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Ganapathy","family":"Ayappa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"issue":"7","key":"349_CR1","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1038\/s41564-020-0701-5","volume":"5","author":"ME Abrams","year":"2020","unstructured":"Abrams ME, Johnson KA, Perelman SS, Zhang L, Endapally S, Mar KB, Thompson BM, McDonald JG, Schoggins JW, Radhakrishnan A et al (2020) Oxysterols provide innate immunity to bacterial infection by mobilizing cell surface accessible cholesterol. Nature Microbiol 5(7):929\u2013942","journal-title":"Nature Microbiol"},{"issue":"8","key":"349_CR2","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.cub.2017.12.034","volume":"28","author":"NW Andrews","year":"2018","unstructured":"Andrews NW, Corrotte M (2018) Plasma membrane repair. Curr Biol 28(8):392\u2013397","journal-title":"Curr Biol"},{"issue":"7","key":"349_CR3","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1021\/acs.biochem.4c00617","volume":"64","author":"S Asthana","year":"2025","unstructured":"Asthana S, Verma A, Bhattacharya B, Nath A, Sajeev N, Maan K, Nair RR, Ayappa KG, Saini DK (2025) Oxysterols modulate protein-sterol interactions to impair CXCR4 signaling in aging cells. Biochemistry. https:\/\/doi.org\/10.1021\/acs.biochem.4c00617","journal-title":"Biochemistry"},{"issue":"18","key":"349_CR4","doi-asserted-by":"publisher","first-page":"3042","DOI":"10.1021\/bi5000096","volume":"53","author":"AA Bielska","year":"2014","unstructured":"Bielska AA, Olsen BN, Gale SE, Mydock-McGrane L, Krishnan K, Baker NA, Schlesinger PH, Covey DF, Ory DS (2014) Side-chain oxysterols modulate cholesterol accessibility through membrane remodeling. Biochemistry 53(18):3042\u20133051","journal-title":"Biochemistry"},{"issue":"16","key":"349_CR5","doi-asserted-by":"publisher","first-page":"3089","DOI":"10.1111\/bph.15073","volume":"178","author":"AJ Brown","year":"2021","unstructured":"Brown AJ, Sharpe LJ, Rogers MJ (2021) Oxysterols: From physiological tuners to pharmacological opportunities. Br J Pharmacol 178(16):3089\u20133103","journal-title":"Br J Pharmacol"},{"issue":"11","key":"349_CR6","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/nri3755","volume":"14","author":"JG Cyster","year":"2014","unstructured":"Cyster JG, Dang EV, Reboldi A, Yi T (2014) 25-hydroxycholesterols in innate and adaptive immunity. Nature Rev Immunol 14(11):731\u2013743","journal-title":"Nature Rev Immunol"},{"issue":"5","key":"349_CR7","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1016\/j.cell.2017.09.029","volume":"171","author":"EV Dang","year":"2017","unstructured":"Dang EV, McDonald JG, Russell DW, Cyster JG (2017) Oxysterol restraint of cholesterol synthesis prevents AIM2 inflammasome activation. Cell 171(5):1057\u20131071","journal-title":"Cell"},{"issue":"26","key":"349_CR8","doi-asserted-by":"publisher","first-page":"10580","DOI":"10.1073\/pnas.1309273110","volume":"110","author":"A Das","year":"2013","unstructured":"Das A, Goldstein JL, Anderson DD, Brown MS, Radhakrishnan A (2013) Use of mutant 125I-perfringolysin O to probe transport and organization of cholesterol in membranes of animal cells. Proc Natl Acad Sci 110(26):10580\u201310585","journal-title":"Proc Natl Acad Sci"},{"key":"349_CR9","doi-asserted-by":"publisher","first-page":"02882","DOI":"10.7554\/eLife.02882","volume":"3","author":"A Das","year":"2014","unstructured":"Das A, Brown MS, Anderson DD, Goldstein JL, Radhakrishnan A (2014) Three pools of plasma membrane cholesterol and their relation to cholesterol homeostasis. eLife 3:02882","journal-title":"eLife"},{"issue":"42","key":"349_CR10","doi-asserted-by":"publisher","first-page":"11496","DOI":"10.1021\/acs.langmuir.7b02277","volume":"33","author":"R Desikan","year":"2017","unstructured":"Desikan R, Maiti PK, Ayappa KG (2017) Assessing the structure and stability of transmembrane oligomeric intermediates of an $$\\alpha$$-helical toxin. Langmuir 33(42):11496\u201311510","journal-title":"Langmuir"},{"key":"349_CR11","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1016\/bs.mie.2021.01.021","volume":"649","author":"R Desikan","year":"2021","unstructured":"Desikan R, Behera A, Maiti PK, Ayappa KG (2021) Using multiscale molecular dynamics simulations to obtain insights into pore forming toxin mechanisms. Methods Enzymol 649:461\u2013502","journal-title":"Methods Enzymol"},{"issue":"5","key":"349_CR12","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1016\/j.cell.2018.12.042","volume":"176","author":"S Endapally","year":"2019","unstructured":"Endapally S, Frias D, Grzemska M, Gay A, Tomchick DR, Radhakrishnan A (2019) Molecular discrimination between two conformations of sphingomyelin in plasma membranes. Cell 176(5):1040\u20131053","journal-title":"Cell"},{"issue":"19","key":"349_CR13","doi-asserted-by":"publisher","first-page":"8577","DOI":"10.1063\/1.470117","volume":"103","author":"U Essmann","year":"1995","unstructured":"Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG (1995) A smooth particle mesh Ewald method. J Phys Chem 103(19):8577\u20138593","journal-title":"J Phys Chem"},{"issue":"1","key":"349_CR14","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1021\/ct700200b","volume":"4","author":"B Hess","year":"2008","unstructured":"Hess B (2008) P-LINCS: A parallel linear constraint solver for molecular simulation. J Chem Theory Comput 4(1):116\u2013122","journal-title":"J Chem Theory Comput"},{"issue":"3","key":"349_CR15","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1021\/ct700301q","volume":"4","author":"B Hess","year":"2008","unstructured":"Hess B, Kutzner C, van der Spoel D, Lindahl E (2008) Gromacs 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 4(3):435\u2013447","journal-title":"J Chem Theory Comput"},{"issue":"3","key":"349_CR16","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1103\/PhysRevA.31.1695","volume":"31","author":"WG Hoover","year":"1985","unstructured":"Hoover WG (1985) Canonical dynamics: Equilibrium phase-space distributions. Phys Rev A 31(3):1695","journal-title":"Phys Rev A"},{"issue":"8","key":"349_CR17","doi-asserted-by":"publisher","first-page":"2938","DOI":"10.1021\/ct300342n","volume":"8","author":"JP Jambeck","year":"2012","unstructured":"Jambeck JP, Lyubartsev AP (2012) An extension and further validation of an all-atomistic force field for biological membranes. J Chem Theory Comput 8(8):2938\u20132948","journal-title":"J Chem Theory Comput"},{"issue":"1","key":"349_CR18","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1021\/ct300777p","volume":"9","author":"JP Jambeck","year":"2013","unstructured":"Jambeck JP, Lyubartsev AP (2013) Another piece of the membrane puzzle: extending Slipids further. J Chem Theory Comput 9(1):774\u2013784","journal-title":"J Chem Theory Comput"},{"key":"349_CR19","doi-asserted-by":"publisher","first-page":"7593","DOI":"10.1039\/D2SM00888B","volume":"18","author":"A Kulshreshtha","year":"2022","unstructured":"Kulshreshtha A, Punnathanam S, Ayappa G (2022) Finite temperature string method with umbrella sampling using path collective variables: Application to secondary structure change in a protein. Soft Matter 18:7593","journal-title":"Soft Matter"},{"issue":"3","key":"349_CR20","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.bpj.2021.11.1129","volume":"121","author":"A Kulshrestha","year":"2022","unstructured":"Kulshrestha A, Maurya S, Gupta T, Roy R, Punnathanam S, Ayappa G (2022) Conformational flexibility is a key determinant of the lytic activity of the pore-forming protein, cytolysin A. Biophys J 121(3):325","journal-title":"Biophys J"},{"issue":"8","key":"349_CR21","doi-asserted-by":"publisher","first-page":"1950","DOI":"10.1002\/prot.22711","volume":"78","author":"K Lindorff-Larsen","year":"2010","unstructured":"Lindorff-Larsen K, Piana S, Palmo K, Maragakis P, Klepeis JL, Dror RO, Shaw DE (2010) Improved side-chain torsion potentials for the Amber ff99sb protein force field. Proteins: Struct Funct Bioinf 78(8):1950\u20131958","journal-title":"Proteins: Struct Funct Bioinf"},{"issue":"2","key":"349_CR22","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1128\/MMBR.00052-12","volume":"77","author":"FC Los","year":"2013","unstructured":"Los FC, Randis TM, Aroian RV, Ratner AJ (2013) Role of pore-forming toxins in bacterial infectious diseases. Microbiol Mol Biol Rev 77(2):173\u2013207","journal-title":"Microbiol Mol Biol Rev"},{"issue":"7247","key":"349_CR23","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1038\/nature08026","volume":"459","author":"M Mueller","year":"2009","unstructured":"Mueller M, Grauschopf U, Maier T, Glockshuber R, Ban N (2009) The structure of a cytolytic $$\\alpha$$-helical toxin pore reveals its assembly mechanism. Nature 459(7247):726\u2013730","journal-title":"Nature"},{"issue":"1","key":"349_CR24","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1063\/1.447334","volume":"81","author":"S Nos\u00e9","year":"1984","unstructured":"Nos\u00e9 S (1984) A unified formulation of the constant temperature molecular dynamics methods. J Phys Chem 81(1):511\u2013519","journal-title":"J Phys Chem"},{"issue":"13","key":"349_CR25","doi-asserted-by":"publisher","first-page":"4854","DOI":"10.1021\/ja8095224","volume":"131","author":"BN Olsen","year":"2009","unstructured":"Olsen BN, Schlesinger PH, Baker NA (2009) Perturbations of membrane structure by cholesterol and cholesterol derivatives are determined by sterol orientation. J Am Chem Soc 131(13):4854\u20134865","journal-title":"J Am Chem Soc"},{"issue":"2","key":"349_CR26","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/j.bbamem.2011.06.014","volume":"1818","author":"BN Olsen","year":"2012","unstructured":"Olsen BN, Schlesinger PH, Ory DS, Baker NA (2012) Side-chain oxysterols: From cells to membranes to molecules. Biochimica et Biophysica Acta (BBA) - Biomembranes 1818(2):330\u2013336","journal-title":"Biochimica et Biophysica Acta (BBA) - Biomembranes"},{"issue":"10","key":"349_CR27","doi-asserted-by":"publisher","first-page":"21889","DOI":"10.1096\/fj.202100036R","volume":"35","author":"TJ Ormsby","year":"2021","unstructured":"Ormsby TJ, Owens SE, Horlock AD, Davies D, Griffiths WJ, Wang Y, Cronin JG, Bromfield JJ, Sheldon IM (2021) Oxysterols protect bovine endometrial cells against pore-forming toxins from pathogenic bacteria. FASEB J 35(10):21889","journal-title":"FASEB J"},{"key":"349_CR28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.815775","volume":"13","author":"TJ Ormsby","year":"2022","unstructured":"Ormsby TJ, Owens SE, Clement L, Mills TJ, Cronin JG, Bromfield JJ, Sheldon IM (2022) Oxysterols protect epithelial cells against pore-forming toxins. Front Immunol 13:815775","journal-title":"Front Immunol"},{"issue":"12","key":"349_CR29","doi-asserted-by":"publisher","first-page":"7182","DOI":"10.1063\/1.328693","volume":"52","author":"M Parrinello","year":"1981","unstructured":"Parrinello M, Rahman A (1981) Polymorphic transitions in single crystals: A new molecular dynamics method. J Appl Phys 52(12):7182\u20137190","journal-title":"J Appl Phys"},{"issue":"2","key":"349_CR30","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/nrmicro.2015.3","volume":"14","author":"MD Peraro","year":"2016","unstructured":"Peraro MD, Van Der Goot FG (2016) Pore-forming toxins: ancient, but never really out of fashion. Nature Rev Microbiol 14(2):77\u201392","journal-title":"Nature Rev Microbiol"},{"issue":"6197","key":"349_CR31","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1126\/science.1254790","volume":"345","author":"A Reboldi","year":"2014","unstructured":"Reboldi A, Dang EV, McDonald JG, Liang G, Russell DW, Cyster JG (2014) 25-hydroxycholesterol suppresses interleukin-1-driven inflammation downstream of type I interferon. Science 345(6197):679\u2013684","journal-title":"Science"},{"issue":"40","key":"349_CR32","doi-asserted-by":"publisher","first-page":"6357","DOI":"10.1021\/bi5007578","volume":"53","author":"D Roderer","year":"2014","unstructured":"Roderer D, Benke S, M\u00fcller M, F\u00e4h-Rechsteiner H, Ban N, Schuler B, Glockshuber R (2014) Characterization of variants of the pore-forming toxin Clya from Escherichia coli controlled by a redox switch. Biochemistry 53(40):6357\u20136369","journal-title":"Biochemistry"},{"issue":"3","key":"349_CR33","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.bpj.2016.11.2833","volume":"112","author":"P Sathyanarayana","year":"2017","unstructured":"Sathyanarayana P, Maurya S, Ayappa G, Visweswariah SS, Roy R (2017) Studying binding, conformational transition and assembly of e.coli cytolysin a pore-forming toxin by single molecule fluorescence. Biophys J 112(3):524","journal-title":"Biophys J"},{"issue":"31","key":"349_CR34","doi-asserted-by":"publisher","first-page":"7323","DOI":"10.1073\/pnas.1721228115","volume":"115","author":"P Sathyanarayana","year":"2018","unstructured":"Sathyanarayana P, Maurya S, Behera A, Ravichandran M, Visweswariah SS, Ayappa KG, Roy R (2018) Cholesterol promotes cytolysin a activity by stabilizing the intermediates during pore formation. Proc Natl Acad Sci 115(31):7323\u20137330","journal-title":"Proc Natl Acad Sci"},{"issue":"1","key":"349_CR35","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1021\/acs.accounts.0c00551","volume":"54","author":"P Sathyanarayana","year":"2020","unstructured":"Sathyanarayana P, Visweswariah SS, Ayappa KG (2020) Mechanistic insights into pore formation by an $$\\alpha$$-pore forming toxin: Protein and lipid bilayer interactions of cytolysin A. Acc Chem Res 54(1):120\u2013131","journal-title":"Acc Chem Res"},{"issue":"10","key":"349_CR36","doi-asserted-by":"publisher","first-page":"6199","DOI":"10.1128\/IAI.73.10.6199-6209.2005","volume":"73","author":"RK Tweten","year":"2005","unstructured":"Tweten RK (2005) Cholesterol-dependent cytolysins, a family of versatile pore-forming toxins. Infect Immun 73(10):6199\u20136209","journal-title":"Infect Immun"},{"issue":"18","key":"349_CR37","doi-asserted-by":"publisher","first-page":"5491","DOI":"10.1128\/JB.185.18.5491-5499.2003","volume":"185","author":"SN Wai","year":"2003","unstructured":"Wai SN, Westermark M, Oscarsson J, Jass J, Maier E, Benz R, Uhlin BE (2003) Characterization of dominantly negative mutant Clya cytotoxin proteins in Escherichia coli. J Bacteriol 185(18):5491\u20135499","journal-title":"J Bacteriol"},{"issue":"7","key":"349_CR38","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1038\/s41590-020-0695-4","volume":"21","author":"QD Zhou","year":"2020","unstructured":"Zhou QD, Chi X, Lee MS, Hsieh WY, Mkrtchyan JJ, Feng A-C, He C, York AG, Bui VL, Kronenberger EB et al (2020) Interferon-mediated reprogramming of membrane cholesterol to evade bacterial toxins. Nature Immunol 21(7):746\u2013755","journal-title":"Nature Immunol"}],"container-title":["The Journal of Membrane Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00232-025-00349-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00232-025-00349-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00232-025-00349-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T18:18:44Z","timestamp":1757182724000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00232-025-00349-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,9]]},"references-count":38,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["349"],"URL":"https:\/\/doi.org\/10.1007\/s00232-025-00349-0","relation":{},"ISSN":["0022-2631","1432-1424"],"issn-type":[{"value":"0022-2631","type":"print"},{"value":"1432-1424","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,9]]},"assertion":[{"value":"15 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}