1shu
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(New page: 200px<br /> <applet load="1shu" size="450" color="white" frame="true" align="right" spinBox="true" caption="1shu, resolution 1.50Å" /> '''Crystal Structure o...)
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Revision as of 17:07, 12 November 2007
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Crystal Structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor
Contents |
Overview
Anthrax toxin is released from Bacillus anthracis as three monomeric, proteins, which assemble into toxic complexes at the surface of, receptor-bearing host cells. One of the proteins, protective antigen (PA), binds to receptors and orchestrates the delivery of the other two (the, lethal and edema factors) into the cytosol. PA has been shown to bind to, two cellular receptors: anthrax toxin receptor/tumor endothelial marker 8, and capillary morphogenesis protein 2 (CMG2). Both are type 1 membrane, proteins that include an approximately 200-aa extracellular von Willebrand, factor A (VWA) domain with a metal ion-dependent adhesion site (MIDAS), motif. The anthrax toxin receptor/tumor endothelial marker 8 and CMG2 VWA, domains share approximately 60% amino acid identity and bind PA directly, in a metal-dependent manner. Here, we report the crystal structure of the, CMG2 VWA domain, with and without its intramolecular disulfide bond, to, 1.5 and 1.8 A, respectively. Both structures contain a carboxylate, ligand-mimetic bound at the MIDAS and appear as open conformations when, compared with the VWA domains from alpha-integrins. The CMG2 structures, provide a template to begin probing the high-affinity CMG2-PA interaction, (200 pM) and may facilitate understanding of toxin, assembly/internalization and the development of new anthrax treatments., The structural data also allow molecular interpretation of known CMG2 VWA, domain mutations linked to the genetic disorders, juvenile hyaline, fibromatosis, and infantile systemic hyalinosis.
Disease
Known diseases associated with this structure: Fibromatosis, juvenile hyaline OMIM:[608041], Hyalinosis, infantile systemic OMIM:[608041]
About this Structure
1SHU is a Single protein structure of sequence from Homo sapiens with MG as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor., Lacy DB, Wigelsworth DJ, Scobie HM, Young JA, Collier RJ, Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6367-72. Epub 2004 Apr 12. PMID:15079089
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