FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4307554461> ?p ?o ?g. }

• W4307554461 abstract "At sites of vascular damage, factor VIII (fVIII) is proteolytically activated by thrombin and binds to activated platelet surfaces with activated factor IX (fIXa) to form the intrinsic tenase complex. Previous structural and mutational studies of fVIII have identified the C1 and C2 domains in binding to negatively charged membrane surfaces through β-hairpin loops with solvent-exposed hydrophobic residues and a ring of positively charged basic residues. Several hemophilia A-associated mutations within the C domains are suggested to disrupt lipid binding, preventing formation of the intrinsic tenase complex. In this study, we devised a novel platform for generating recombinant C1, C2, and C1C2 domain constructs and performed mutagenesis of several charged residues proximal to the putative membrane binding region of each C domain. Binding measurements between phosphatidylserine (PS)-containing lipid membrane surfaces and fVIII C domains demonstrated an ionic strength dependence on membrane binding affinity. Mutations to basic residues adjacent to the surface-exposed hydrophobic regions of C1 and C2 differentially disrupted membrane binding, with abrogation of binding occurring for mutations to conserved arginine residues in the C1 (R2163) and C2 (R2320) domains. Lastly, we determined the X-ray crystal structure of the porcine fVIII C2 domain bound to o-phospho-L-serine, the polar headgroup of PS, which binds to a basic cleft and makes charge-charge contact with R2320. We conclude that basic clefts in the fVIII C domains bind to PS-containing membranes through conserved arginine residues via a C domain modularity, where each C domain possesses modest electrostatic-dependent affinity and tandem C domains are required for high affinity binding." @default.
• W4307554461 created "2022-11-03" @default.
• W4307554461 creator A5009440693 @default.
• W4307554461 creator A5024239657 @default.
• W4307554461 creator A5027437535 @default.
• W4307554461 creator A5033082394 @default.
• W4307554461 creator A5046933314 @default.
• W4307554461 creator A5048559217 @default.
• W4307554461 creator A5052396874 @default.
• W4307554461 creator A5075710353 @default.
• W4307554461 creator A5082955813 @default.
• W4307554461 creator A5085339261 @default.
• W4307554461 date "2022-10-26" @default.
• W4307554461 modified "2023-09-27" @default.
• W4307554461 title "Stable binding to phosphatidylserine-containing membranes requires conserved arginine residues in tandem C domains of blood coagulation factor VIII" @default.
• W4307554461 cites W1494429407 @default.
• W4307554461 cites W1627916641 @default.
• W4307554461 cites W1803226853 @default.
• W4307554461 cites W1891870091 @default.
• W4307554461 cites W1928245215 @default.
• W4307554461 cites W1936207504 @default.
• W4307554461 cites W1980012853 @default.
• W4307554461 cites W1990696306 @default.
• W4307554461 cites W1998679864 @default.
• W4307554461 cites W2006836982 @default.
• W4307554461 cites W2009736469 @default.
• W4307554461 cites W2014561247 @default.
• W4307554461 cites W2016141667 @default.
• W4307554461 cites W2017471463 @default.
• W4307554461 cites W2018292694 @default.
• W4307554461 cites W2025760623 @default.
• W4307554461 cites W20271833 @default.
• W4307554461 cites W2033021781 @default.
• W4307554461 cites W2038591666 @default.
• W4307554461 cites W2044694095 @default.
• W4307554461 cites W2062628301 @default.
• W4307554461 cites W2066775733 @default.
• W4307554461 cites W2067564649 @default.
• W4307554461 cites W2068033906 @default.
• W4307554461 cites W2092435695 @default.
• W4307554461 cites W2095498248 @default.
• W4307554461 cites W2096747438 @default.
• W4307554461 cites W2105300484 @default.
• W4307554461 cites W2108921801 @default.
• W4307554461 cites W2123873984 @default.
• W4307554461 cites W2124026197 @default.
• W4307554461 cites W2143320896 @default.
• W4307554461 cites W2148653123 @default.
• W4307554461 cites W2151938814 @default.
• W4307554461 cites W2152737925 @default.
• W4307554461 cites W2154181324 @default.
• W4307554461 cites W2180229411 @default.
• W4307554461 cites W2278120109 @default.
• W4307554461 cites W2414027291 @default.
• W4307554461 cites W2569325116 @default.
• W4307554461 cites W2910822860 @default.
• W4307554461 cites W2922370844 @default.
• W4307554461 cites W2970865235 @default.
• W4307554461 cites W2990552556 @default.
• W4307554461 cites W4230625605 @default.
• W4307554461 cites W4232006196 @default.
• W4307554461 cites W4249629479 @default.
• W4307554461 cites W4297820747 @default.
• W4307554461 cites W62994428 @default.
• W4307554461 doi "https://doi.org/10.3389/fmolb.2022.1040106" @default.
• W4307554461 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36387287" @default.
• W4307554461 hasPublicationYear "2022" @default.
• W4307554461 type Work @default.
• W4307554461 citedByCount "0" @default.
• W4307554461 crossrefType "journal-article" @default.
• W4307554461 hasAuthorship W4307554461A5009440693 @default.
• W4307554461 hasAuthorship W4307554461A5024239657 @default.
• W4307554461 hasAuthorship W4307554461A5027437535 @default.
• W4307554461 hasAuthorship W4307554461A5033082394 @default.
• W4307554461 hasAuthorship W4307554461A5046933314 @default.
• W4307554461 hasAuthorship W4307554461A5048559217 @default.
• W4307554461 hasAuthorship W4307554461A5052396874 @default.
• W4307554461 hasAuthorship W4307554461A5075710353 @default.
• W4307554461 hasAuthorship W4307554461A5082955813 @default.
• W4307554461 hasAuthorship W4307554461A5085339261 @default.
• W4307554461 hasBestOaLocation W43075544611 @default.
• W4307554461 hasConcept C107824862 @default.
• W4307554461 hasConcept C12554922 @default.
• W4307554461 hasConcept C143840085 @default.
• W4307554461 hasConcept C185592680 @default.
• W4307554461 hasConcept C203014093 @default.
• W4307554461 hasConcept C2777292125 @default.
• W4307554461 hasConcept C2777444498 @default.
• W4307554461 hasConcept C2777468819 @default.
• W4307554461 hasConcept C2778918659 @default.
• W4307554461 hasConcept C2779637612 @default.
• W4307554461 hasConcept C41625074 @default.
• W4307554461 hasConcept C47701112 @default.
• W4307554461 hasConcept C515207424 @default.
• W4307554461 hasConcept C51639874 @default.
• W4307554461 hasConcept C55493867 @default.
• W4307554461 hasConcept C86803240 @default.
• W4307554461 hasConcept C89560881 @default.
• W4307554461 hasConceptScore W4307554461C107824862 @default.
• W4307554461 hasConceptScore W4307554461C12554922 @default.

• next