Structure of the fibrinogen gamma-chain integrin binding and factor XIIIa cross-linking sites obtained through carrier protein driven crystallization.
The human fibrinogen gamma-chain C-terminal segment functions as the platelet integrin binding site as well as the Factor XIIIa cross-linking substrate and thus plays an important role in blood clot formation and stabilization. The three-dimensional structure of this segment has been determined using carrier protein driven crystallization. The C-terminal segment, gamma-(398-411), was attached to a linker sequence at the C-terminus of glutathione S-transferase and the structure of this fusion protein determined at 1.8 A resolution. Functional studies of the chimeric protein demonstrate that the fibrinogen sequence in the presence of the carrier protein retains its specific functions as ligand for platelet integrin alpha(IIb)beta3 (gpIIb/IIIa) and as a cross-linking substrate for Factor XIIIa. The structure obtained for the fibrinogen gamma-chain segment is not affected by crystal packing and can provide the missing links to the recently reported model of cross-linked fibrin.
Ware
S
S
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Donahue
J P
JP
Hawiger
J
J
Anderson
W F
WF
D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D003460:Crystallization; D005340:Fibrinogen / Q000737:chemistry* / Q000235:genetics; D005982:Glutathione Transferase / Q000737:chemistry / Q000235:genetics; D006801:Humans; D016023:Integrins / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D012549:Schistosoma japonicum / Q000737:chemistry; D011503:Transglutaminases / Q000737:chemistry*; D014961:X-Ray Diffraction
D002352:Carrier Proteins; D003432:Cross-Linking Reagents; D016023:Integrins; D011993:Recombinant Fusion Proteins; D005340:Fibrinogen; D011503:Transglutaminases; D005982:Glutathione Transferase