Crystal structure of the von Willebrand factor modulator botrocetin.
The binding of von Willebrand factor (vWF) to the platelet receptor, glycoprotein (GP) Ib-IX-V complex, has a key role in the initiation of thrombus formation and is regulated by interactions with extracellular matrix components under the influence of hemodynamic forces. To a certain extent, these effects can be mimicked in vitro by two nonphysiologic modulators, ristocetin and botrocetin. The latter, isolated from the venom of the snake Bothrops jararaca, is a 31-kDa heterodimeric protein that forms a soluble complex with vWF. As an initial step toward understanding the mechanisms that regulate vWF function, we have solved the crystal structure of botrocetin at 1.8 A resolution. Botrocetin exhibits homology with other snake proteins, but contains only one metal binding site as compared to two in Factor IX binding protein and Factor IX/X binding protein and none in flavocetin. A distinctive feature of botrocetin is the presence of a negatively charged surface that may play a role in the association with the vWF A1 domain.
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Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Vasudevan
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Subbarao
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McClintock
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Celikel
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Ruggeri
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Varughese
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D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D003435:Crotalid Venoms / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D003460:Crystallization; D018360:Crystallography, X-Ray; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry; D005164:Factor IX / Q000378:metabolism; D005170:Factor X / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D037102:Lectins / Q000737:chemistry / Q000378:metabolism; D037181:Lectins, C-Type; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D030162:Reptilian Proteins; D017386:Sequence Homology, Amino Acid; D013499:Surface Properties; D014841:von Willebrand Factor / Q000378:metabolism* / Q000502:physiology
D002352:Carrier Proteins; D002413:Cations, Divalent; D003435:Crotalid Venoms; D004220:Disulfides; D037102:Lectins; D037181:Lectins, C-Type; D030162:Reptilian Proteins; D014841:von Willebrand Factor; C070302:factor IX-factor X-binding protein, Crotalinae; C030961:botrocetin; D005164:Factor IX; D005170:Factor X; D008274:Magnesium