FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2036307682> ?p ?o ?g. }

• W2036307682 endingPage "400" @default.
• W2036307682 startingPage "393" @default.
• W2036307682 abstract "Complex formation between coagulation factor VIII (FVIII) and von Willebrand factor (VWF) is of critical importance to protect FVIII from rapid in vivo clearance and degradation. We have now employed a chemical footprinting approach to identify regions on VWF involved in FVIII binding. To this end, lysine amino acid residues of VWF were chemically modified in the presence of FVIII or activated FVIII, which does not bind VWF. Nano-LC-MS analysis showed that the lysine residues of almost all identified VWF peptides were not differentially modified upon incubation of VWF with FVIII or activated FVIII. However, Lys-773 of peptide Ser-766–Leu-774 was protected from chemical modification in the presence of FVIII. In addition, peptide Ser-764–Arg-782, which comprises the first 19 amino acid residues of mature VWF, showed a differential modification of both Lys-773 and the α-amino group of Ser-764. To verify the role of Lys-773 and the N-terminal Ser-764 in FVIII binding, we employed VWF variants in which either Lys-773 or Ser-764 was replaced with Ala. Surface plasmon resonance analysis and competition studies revealed that VWF(K773A) exhibited reduced binding to FVIII and the FVIII light chain, which harbors the VWF-binding site. In contrast, VWF(S764A) revealed more effective binding to FVIII and the FVIII light chain compared with WT VWF. The results of our study show that the N terminus of VWF is critical for the interaction with FVIII and that Ser-764 and Lys-773 have opposite roles in the binding mechanism. Complex formation between coagulation factor VIII (FVIII) and von Willebrand factor (VWF) is of critical importance to protect FVIII from rapid in vivo clearance and degradation. We have now employed a chemical footprinting approach to identify regions on VWF involved in FVIII binding. To this end, lysine amino acid residues of VWF were chemically modified in the presence of FVIII or activated FVIII, which does not bind VWF. Nano-LC-MS analysis showed that the lysine residues of almost all identified VWF peptides were not differentially modified upon incubation of VWF with FVIII or activated FVIII. However, Lys-773 of peptide Ser-766–Leu-774 was protected from chemical modification in the presence of FVIII. In addition, peptide Ser-764–Arg-782, which comprises the first 19 amino acid residues of mature VWF, showed a differential modification of both Lys-773 and the α-amino group of Ser-764. To verify the role of Lys-773 and the N-terminal Ser-764 in FVIII binding, we employed VWF variants in which either Lys-773 or Ser-764 was replaced with Ala. Surface plasmon resonance analysis and competition studies revealed that VWF(K773A) exhibited reduced binding to FVIII and the FVIII light chain, which harbors the VWF-binding site. In contrast, VWF(S764A) revealed more effective binding to FVIII and the FVIII light chain compared with WT VWF. The results of our study show that the N terminus of VWF is critical for the interaction with FVIII and that Ser-764 and Lys-773 have opposite roles in the binding mechanism." @default.
• W2036307682 created "2016-06-24" @default.
• W2036307682 creator A5014325722 @default.
• W2036307682 creator A5026414692 @default.
• W2036307682 creator A5042863699 @default.
• W2036307682 creator A5045729019 @default.
• W2036307682 creator A5056038004 @default.
• W2036307682 creator A5074112020 @default.
• W2036307682 creator A5082243444 @default.
• W2036307682 date "2013-01-01" @default.
• W2036307682 modified "2023-09-28" @default.
• W2036307682 title "Distinct Roles of Ser-764 and Lys-773 at the N Terminus of von Willebrand Factor in Complex Assembly with Coagulation Factor VIII" @default.
• W2036307682 cites W1494526055 @default.
• W2036307682 cites W1512481003 @default.
• W2036307682 cites W1539663343 @default.
• W2036307682 cites W1542837635 @default.
• W2036307682 cites W1566177450 @default.
• W2036307682 cites W174752904 @default.
• W2036307682 cites W1974389101 @default.
• W2036307682 cites W1980884659 @default.
• W2036307682 cites W1990942416 @default.
• W2036307682 cites W2002741069 @default.
• W2036307682 cites W2016112642 @default.
• W2036307682 cites W2025238197 @default.
• W2036307682 cites W2027217170 @default.
• W2036307682 cites W2040257513 @default.
• W2036307682 cites W2042983726 @default.
• W2036307682 cites W2044174464 @default.
• W2036307682 cites W2044694095 @default.
• W2036307682 cites W2045931072 @default.
• W2036307682 cites W2049786448 @default.
• W2036307682 cites W2065110399 @default.
• W2036307682 cites W2065167801 @default.
• W2036307682 cites W2067564649 @default.
• W2036307682 cites W2071018055 @default.
• W2036307682 cites W2095498248 @default.
• W2036307682 cites W211967407 @default.
• W2036307682 cites W2127451188 @default.
• W2036307682 cites W2129977314 @default.
• W2036307682 cites W2137827663 @default.
• W2036307682 cites W2141987196 @default.
• W2036307682 cites W2337186576 @default.
• W2036307682 cites W2409286460 @default.
• W2036307682 cites W2411945890 @default.
• W2036307682 cites W262805330 @default.
• W2036307682 cites W299020133 @default.
• W2036307682 cites W72493355 @default.
• W2036307682 cites W95014119 @default.
• W2036307682 doi "https://doi.org/10.1074/jbc.m112.400572" @default.
• W2036307682 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3537036" @default.
• W2036307682 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23168412" @default.
• W2036307682 hasPublicationYear "2013" @default.
• W2036307682 type Work @default.
• W2036307682 sameAs 2036307682 @default.
• W2036307682 citedByCount "15" @default.
• W2036307682 countsByYear W20363076822013 @default.
• W2036307682 countsByYear W20363076822014 @default.
• W2036307682 countsByYear W20363076822015 @default.
• W2036307682 countsByYear W20363076822018 @default.
• W2036307682 countsByYear W20363076822019 @default.
• W2036307682 countsByYear W20363076822021 @default.
• W2036307682 countsByYear W20363076822022 @default.
• W2036307682 crossrefType "journal-article" @default.
• W2036307682 hasAuthorship W2036307682A5014325722 @default.
• W2036307682 hasAuthorship W2036307682A5026414692 @default.
• W2036307682 hasAuthorship W2036307682A5042863699 @default.
• W2036307682 hasAuthorship W2036307682A5045729019 @default.
• W2036307682 hasAuthorship W2036307682A5056038004 @default.
• W2036307682 hasAuthorship W2036307682A5074112020 @default.
• W2036307682 hasAuthorship W2036307682A5082243444 @default.
• W2036307682 hasBestOaLocation W20363076821 @default.
• W2036307682 hasConcept C107824862 @default.
• W2036307682 hasConcept C126322002 @default.
• W2036307682 hasConcept C150903083 @default.
• W2036307682 hasConcept C153911025 @default.
• W2036307682 hasConcept C185592680 @default.
• W2036307682 hasConcept C203014093 @default.
• W2036307682 hasConcept C207001950 @default.
• W2036307682 hasConcept C2776016237 @default.
• W2036307682 hasConcept C2778382381 @default.
• W2036307682 hasConcept C2778780528 @default.
• W2036307682 hasConcept C2779281246 @default.
• W2036307682 hasConcept C2779394231 @default.
• W2036307682 hasConcept C515207424 @default.
• W2036307682 hasConcept C55493867 @default.
• W2036307682 hasConcept C71924100 @default.
• W2036307682 hasConcept C86803240 @default.
• W2036307682 hasConcept C89560881 @default.
• W2036307682 hasConceptScore W2036307682C107824862 @default.
• W2036307682 hasConceptScore W2036307682C126322002 @default.
• W2036307682 hasConceptScore W2036307682C150903083 @default.
• W2036307682 hasConceptScore W2036307682C153911025 @default.
• W2036307682 hasConceptScore W2036307682C185592680 @default.
• W2036307682 hasConceptScore W2036307682C203014093 @default.
• W2036307682 hasConceptScore W2036307682C207001950 @default.
• W2036307682 hasConceptScore W2036307682C2776016237 @default.
• W2036307682 hasConceptScore W2036307682C2778382381 @default.
• W2036307682 hasConceptScore W2036307682C2778780528 @default.

• next