1shu
From Proteopedia
(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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| - | [[Image:1shu.gif|left|200px]]<br /> | + | [[Image:1shu.gif|left|200px]]<br /><applet load="1shu" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1shu, resolution 1.50Å" /> | caption="1shu, resolution 1.50Å" /> | ||
'''Crystal Structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor'''<br /> | '''Crystal Structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Anthrax toxin is released from Bacillus anthracis as three monomeric | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1SHU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1SHU is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SHU OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Collier, R | + | [[Category: Collier, R J.]] |
| - | [[Category: Lacy, D | + | [[Category: Lacy, D B.]] |
| - | [[Category: Scobie, H | + | [[Category: Scobie, H M.]] |
| - | [[Category: Wigelsworth, D | + | [[Category: Wigelsworth, D J.]] |
| - | [[Category: Young, J | + | [[Category: Young, J A.T.]] |
[[Category: MG]] | [[Category: MG]] | ||
[[Category: alpha/beta rossmann fold]] | [[Category: alpha/beta rossmann fold]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:01:39 2008'' |
Revision as of 13:01, 21 February 2008
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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 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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