View source for 1shu


==Crystal Structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor==
<StructureSection load='1shu' size='340' side='right'caption='[[1shu]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1shu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SHU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1shu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1shu OCA], [https://pdbe.org/1shu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1shu RCSB], [https://www.ebi.ac.uk/pdbsum/1shu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1shu ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/ANTR2_HUMAN ANTR2_HUMAN] Defects in ANTXR2 are the cause of infantile systemic hyalinosis (ISH) [MIM:[https://omim.org/entry/236490 236490]. This autosomal recessive syndrome is similar to JHF, but has an earlier onset and a more severe course. Symptoms appear at birth or within the first months of life, with painful, swollen joint contractures, osteopenia, osteoporosis and livid red hyperpigmentation over bony prominences. Patients develop multiple subcutaneous skin tumors and gingival hypertrophy. Hyaline deposits in multiple organs, recurrent infections and intractable diarrhea often lead to death within the first 2 years of life. Surviving children may suffer from severely reduced mobility due to joint contractures.<ref>PMID:12973667</ref> <ref>PMID:14508707</ref>   Defects in ANTXR2 are the cause of juvenile hyaline fibromatosis (JHF) [MIM:[https://omim.org/entry/228600 228600]. JHF is an autosomal recessive syndrome that is similar to ISH but takes a milder course. It is characterized by hyaline deposition in the dermis, multiple subcutaneous skin tumors and gingival hypertrophy, followed by progressive joint contractions, osteopenia and osteoporosis that may lead to a severe limitation of mobility.<ref>PMID:12973667</ref> <ref>PMID:14508707</ref> 
== Function ==
[https://www.uniprot.org/uniprot/ANTR2_HUMAN ANTR2_HUMAN] Necessary for cellular interactions with laminin and the extracellular matrix.<ref>PMID:11683410</ref> <ref>PMID:12973667</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sh/1shu_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1shu ConSurf].
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== Publication Abstract from PubMed ==
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.

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<ref>PMID:15079089</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Collier RJ]]
[[Category: Lacy DB]]
[[Category: Scobie HM]]
[[Category: Wigelsworth DJ]]
[[Category: Young JAT]]