title: Crystal structure of the von Willebrand factor modulator botrocetin.
abstract: 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.
authors.affiliation: 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.
authors.forename: U
authors.initials: U
authors.lastname: Sen
authors.forename: S
authors.initials: S
authors.lastname: Vasudevan
authors.forename: G
authors.initials: G
authors.lastname: Subbarao
authors.forename: R A
authors.initials: RA
authors.lastname: McClintock
authors.forename: R
authors.initials: R
authors.lastname: Celikel
authors.forename: Z M
authors.initials: ZM
authors.lastname: Ruggeri
authors.forename: K I
authors.initials: KI
authors.lastname: Varughese
mesh_terms: 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
chemical_list: 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