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U.S.A."],"published-print":{"date-parts":[[2026,9,8]]},"abstract":"<jats:p>Phosphatidylserine on the surface of activated cells serves as a signal for coagulation factor binding and the membrane-dependent assembly of enzyme complexes that drive the accelerated host response to vascular damage. Here, we use single-particle cryo-EM of liposome-bound proteins to establish common mechanisms utilized by coagulation factors V and VIII for membrane binding and phospholipid specificity. The interface between these peripheral proteins and the membrane shows contacts between the discoidin C1 and C2 domains and the interfacial phospholipid headgroup region of the membrane bilayer. There is no evidence for the insertion of membrane-contacting protein loops into the membrane core. This refutes previous models of high affinity protein binding by insertion into the hydrophobic core of the membrane. We also resolve density for the headgroup of phosphatidylserine bound to conserved pockets within the C1 and C2 domains. These single binding pockets in each C domain highlight the network of putative hydrogen bonds that contribute to binding specificity for phosphatidylserine. Our results now provide a high-resolution structural view of the protein\u2013membrane interface for these coagulation proteins and highlight the utility of using liposomes as near-physiologic membrane mimetics in structural studies. The principles established in this work may also apply to other biological systems wherein function is regulated by reversible membrane binding.<\/jats:p>","DOI":"10.1073\/pnas.2622255123","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:36:43Z","timestamp":1788370603000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Structural basis for membrane binding by coagulation factors V and VIII and their specificity for phosphatidylserine-containing membranes"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4008-2461","authenticated-orcid":false,"given":"Vladimir N.","family":"Kolyadko","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01z7r7q48","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Hematology, Department of Pediatrics, Children\u2019s Hospital of 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