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1sht

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Revision as of 10:20, 25 January 2015

Crystal Structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor

Structural highlights

1sht is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1shv
Gene:	ANTXR2, CMG2 (HUMAN)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[ANTR2_HUMAN] Defects in ANTXR2 are the cause of infantile systemic hyalinosis (ISH) [MIM: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.^[1] ^[2] Defects in ANTXR2 are the cause of juvenile hyaline fibromatosis (JHF) [MIM: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.^[3] ^[4]

Function

[ANTR2_HUMAN] Necessary for cellular interactions with laminin and the extracellular matrix.^[5] ^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Dowling O, Difeo A, Ramirez MC, Tukel T, Narla G, Bonafe L, Kayserili H, Yuksel-Apak M, Paller AS, Norton K, Teebi AS, Grum-Tokars V, Martin GS, Davis GE, Glucksman MJ, Martignetti JA. Mutations in capillary morphogenesis gene-2 result in the allelic disorders juvenile hyaline fibromatosis and infantile systemic hyalinosis. Am J Hum Genet. 2003 Oct;73(4):957-66. Epub 2003 Sep 12. PMID:12973667 doi:http://dx.doi.org/S0002-9297(07)63642-8
↑ Hanks S, Adams S, Douglas J, Arbour L, Atherton DJ, Balci S, Bode H, Campbell ME, Feingold M, Keser G, Kleijer W, Mancini G, McGrath JA, Muntoni F, Nanda A, Teare MD, Warman M, Pope FM, Superti-Furga A, Futreal PA, Rahman N. Mutations in the gene encoding capillary morphogenesis protein 2 cause juvenile hyaline fibromatosis and infantile systemic hyalinosis. Am J Hum Genet. 2003 Oct;73(4):791-800. Epub 2003 Aug 21. PMID:14508707 doi:S0002-9297(07)63628-3
↑ Dowling O, Difeo A, Ramirez MC, Tukel T, Narla G, Bonafe L, Kayserili H, Yuksel-Apak M, Paller AS, Norton K, Teebi AS, Grum-Tokars V, Martin GS, Davis GE, Glucksman MJ, Martignetti JA. Mutations in capillary morphogenesis gene-2 result in the allelic disorders juvenile hyaline fibromatosis and infantile systemic hyalinosis. Am J Hum Genet. 2003 Oct;73(4):957-66. Epub 2003 Sep 12. PMID:12973667 doi:http://dx.doi.org/S0002-9297(07)63642-8
↑ Hanks S, Adams S, Douglas J, Arbour L, Atherton DJ, Balci S, Bode H, Campbell ME, Feingold M, Keser G, Kleijer W, Mancini G, McGrath JA, Muntoni F, Nanda A, Teare MD, Warman M, Pope FM, Superti-Furga A, Futreal PA, Rahman N. Mutations in the gene encoding capillary morphogenesis protein 2 cause juvenile hyaline fibromatosis and infantile systemic hyalinosis. Am J Hum Genet. 2003 Oct;73(4):791-800. Epub 2003 Aug 21. PMID:14508707 doi:S0002-9297(07)63628-3
↑ Bell SE, Mavila A, Salazar R, Bayless KJ, Kanagala S, Maxwell SA, Davis GE. Differential gene expression during capillary morphogenesis in 3D collagen matrices: regulated expression of genes involved in basement membrane matrix assembly, cell cycle progression, cellular differentiation and G-protein signaling. J Cell Sci. 2001 Aug;114(Pt 15):2755-73. PMID:11683410
↑ Dowling O, Difeo A, Ramirez MC, Tukel T, Narla G, Bonafe L, Kayserili H, Yuksel-Apak M, Paller AS, Norton K, Teebi AS, Grum-Tokars V, Martin GS, Davis GE, Glucksman MJ, Martignetti JA. Mutations in capillary morphogenesis gene-2 result in the allelic disorders juvenile hyaline fibromatosis and infantile systemic hyalinosis. Am J Hum Genet. 2003 Oct;73(4):957-66. Epub 2003 Sep 12. PMID:12973667 doi:http://dx.doi.org/S0002-9297(07)63642-8
↑ Lacy DB, Wigelsworth DJ, Scobie HM, Young JA, Collier RJ. Crystal structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6367-72. Epub 2004 Apr 12. PMID:15079089 doi:10.1073/pnas.0401506101

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1sht"

@@ Line 2: / Line 2: @@
 <StructureSection load='1sht' size='340' side='right' caption='[[1sht]], [[Resolution|resolution]] 1.81&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1sht]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SHT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1SHT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1sht]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SHT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1SHT FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1shv|1shv]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ANTXR2, CMG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1sht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sht OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1sht RCSB], [http://www.ebi.ac.uk/pdbsum/1sht PDBsum]</span></td></tr>
 </table>
@@ Line 33: / Line 34: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Collier, R J]]
 [[Category: Lacy, D B]]

1sht

From Proteopedia

Revision as of 10:20, 25 January 2015

Crystal Structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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