A1 DOMAIN OF VON WILLEBRAND FACTOR COMPLEXES; AND BACTERIAL SIGNAL TRANSDUCTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Binding of the platelet membrane glycoprotein (GP) Ibalpha to von Willebrand Factor (vWF) immobilized on the vessel wall initiates thrombus formation. This process, essential to arrest bleeding at wound sites, may also contribute to thrombotic diseases such as myocardial infarction, and is modulated by the affinity of vWF for platelets. At wall shear rates of 1500 s^(-1) or greater, platelet tethering to extracellular matrix components and thrombus growth depend on GP Ibalpha binding to the vWF A1 domain. We have determined the crystal structures the A1 domain of vWF and a modulator of A1 domain function- a snake venom protein, botrocetin. Now we have collected Pt MAD data on the platelet membrane receptor GP Ibalpha and the model building is in progress. We are in the process of crystallizing complexes of the GP Ibalpha with the A1 domain and the modulator botrocetin. 2. Bacterial phosphorelay proteins are investigated. Recently we solved the structure of the transcription factor Spo0A from B. subtilis in complex with a DNA duplex containing the recognition sequence. Crystallization of the transcription factor in complex with other promotor sequences are in progress. Spo0A initiates sporulation. Anthrax is caused by B. anthracis and its transcription factor is almost identical with that of B. subtilis.