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| | ==The Crystal Structure of Tumor Endothelial Marker 8 (TEM8) extracellular domain== | | ==The Crystal Structure of Tumor Endothelial Marker 8 (TEM8) extracellular domain== |
| - | <StructureSection load='3n2n' size='340' side='right' caption='[[3n2n]], [[Resolution|resolution]] 1.80Å' scene=''> | + | <StructureSection load='3n2n' size='340' side='right'caption='[[3n2n]], [[Resolution|resolution]] 1.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3n2n]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N2N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N2N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3n2n]] is a 6 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=3N2N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N2N 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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ANTXR1, ATR, TEM8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3n2n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n2n OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3n2n RCSB], [http://www.ebi.ac.uk/pdbsum/3n2n PDBsum]</span></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=3n2n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n2n OCA], [https://pdbe.org/3n2n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n2n RCSB], [https://www.ebi.ac.uk/pdbsum/3n2n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n2n ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/ANTR1_HUMAN ANTR1_HUMAN]] Defects in ANTXR1 are associated with susceptibility to hemangioma capillary infantile (HCI) [MIM:[http://omim.org/entry/602089 602089]]. HCI are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. They are the most common tumor of infancy, occurring in up to 10% of all births. Hemangiomas tend to appear shortly after birth and show rapid neonatal growth for up to 12 months characterized by endothelial hypercellularity and increased numbers of mast cells. This phase is followed by slow involution at a rate of about 10% per year and replacement by fibrofatty stroma.<ref>PMID:18931684</ref> | + | [https://www.uniprot.org/uniprot/ANTR1_HUMAN ANTR1_HUMAN] Defects in ANTXR1 are associated with susceptibility to hemangioma capillary infantile (HCI) [MIM:[https://omim.org/entry/602089 602089]. HCI are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. They are the most common tumor of infancy, occurring in up to 10% of all births. Hemangiomas tend to appear shortly after birth and show rapid neonatal growth for up to 12 months characterized by endothelial hypercellularity and increased numbers of mast cells. This phase is followed by slow involution at a rate of about 10% per year and replacement by fibrofatty stroma.<ref>PMID:18931684</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ANTR1_HUMAN ANTR1_HUMAN]] Plays a role in cell attachment and migration. Interacts with extracellular matrix proteins and with the actin cytoskeleton. Mediates adhesion of cells to type 1 collagen and gelatin, reorganization of the actin cytoskeleton and promotes cell spreading. Plays a role in the angiogenic response of cultured umbilical vein endothelial cells.<ref>PMID:15777794</ref> <ref>PMID:16762926</ref> | + | [https://www.uniprot.org/uniprot/ANTR1_HUMAN ANTR1_HUMAN] Plays a role in cell attachment and migration. Interacts with extracellular matrix proteins and with the actin cytoskeleton. Mediates adhesion of cells to type 1 collagen and gelatin, reorganization of the actin cytoskeleton and promotes cell spreading. Plays a role in the angiogenic response of cultured umbilical vein endothelial cells.<ref>PMID:15777794</ref> <ref>PMID:16762926</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3n2n" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Fu, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Li, Y Y]] | + | [[Category: Fu S]] |
| - | [[Category: Rao, Z H]] | + | [[Category: Li YY]] |
| - | [[Category: Tong, X H]] | + | [[Category: Rao ZH]] |
| - | [[Category: Wu, Y]] | + | [[Category: Tong XH]] |
| - | [[Category: Anthrax]]
| + | [[Category: Wu Y]] |
| - | [[Category: Rossmann fold]]
| + | |
| - | [[Category: Toxin receptor]]
| + | |
| Structural highlights
Disease
ANTR1_HUMAN Defects in ANTXR1 are associated with susceptibility to hemangioma capillary infantile (HCI) [MIM:602089. HCI are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. They are the most common tumor of infancy, occurring in up to 10% of all births. Hemangiomas tend to appear shortly after birth and show rapid neonatal growth for up to 12 months characterized by endothelial hypercellularity and increased numbers of mast cells. This phase is followed by slow involution at a rate of about 10% per year and replacement by fibrofatty stroma.[1]
Function
ANTR1_HUMAN Plays a role in cell attachment and migration. Interacts with extracellular matrix proteins and with the actin cytoskeleton. Mediates adhesion of cells to type 1 collagen and gelatin, reorganization of the actin cytoskeleton and promotes cell spreading. Plays a role in the angiogenic response of cultured umbilical vein endothelial cells.[2] [3]
Publication Abstract from PubMed
Anthrax toxin, which is released from the gram-positive bacterium Bacillus anthracis, is composed of three proteins: protective antigen (PA), lethal factor (LF), and edema factor (EF). PA binds a receptor on the surface of the target cell and further assembles into a homo-heptameric pore through which EF and LF translocate into the cytosol. Two distinct cellular receptors for anthrax toxin, TEM8/ANTXR1 and CMG2/ANTXR2, have been identified, and it is known that their extracellular domains bind PA with low and high affinities, respectively. Here, we report the crystal structure of the TEM8 extracellular vWA domain at 1.7 A resolution. The overall structure has a typical integrin fold and is similar to that of the previously published CMG2 structure. In addition, using structure-based mutagenesis, we demonstrate that the putative interface region of TEM8 with PA (consisting of residues 56, 57, and 154-160) is responsible for the PA-binding affinity differences between the two receptors. In particular, Leu56 was shown to be a key factor for the lower affinity of TEM8 towards PA compared with CMG2. Because of its high affinity for PA and low expression in normal tissues, an isolated extracellular vWA domain of the L56A TEM8 variant may serve as a potent antitoxin and a potential therapeutic treatment for anthrax infection. Moreover, as TEM8 is often over-expressed in tumor cells, our TEM8 crystal structure may provide new insights into how to design PA mutants that preferentially target tumor cells.
The structure of tumor endothelial marker 8 (TEM8) extracellular domain and implications for its receptor function for recognizing anthrax toxin.,Fu S, Tong X, Cai C, Zhao Y, Wu Y, Li Y, Xu J, Zhang XC, Xu L, Chen W, Rao Z PLoS One. 2010 Jun 18;5(6):e11203. PMID:20585457[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jinnin M, Medici D, Park L, Limaye N, Liu Y, Boscolo E, Bischoff J, Vikkula M, Boye E, Olsen BR. Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangioma. Nat Med. 2008 Nov;14(11):1236-46. doi: 10.1038/nm.1877. Epub 2008 Oct 19. PMID:18931684 doi:10.1038/nm.1877
- ↑ Hotchkiss KA, Basile CM, Spring SC, Bonuccelli G, Lisanti MP, Terman BI. TEM8 expression stimulates endothelial cell adhesion and migration by regulating cell-matrix interactions on collagen. Exp Cell Res. 2005 Apr 15;305(1):133-44. PMID:15777794 doi:10.1016/j.yexcr.2004.12.025
- ↑ Werner E, Kowalczyk AP, Faundez V. Anthrax toxin receptor 1/tumor endothelium marker 8 mediates cell spreading by coupling extracellular ligands to the actin cytoskeleton. J Biol Chem. 2006 Aug 11;281(32):23227-36. Epub 2006 Jun 8. PMID:16762926 doi:10.1074/jbc.M603676200
- ↑ Fu S, Tong X, Cai C, Zhao Y, Wu Y, Li Y, Xu J, Zhang XC, Xu L, Chen W, Rao Z. The structure of tumor endothelial marker 8 (TEM8) extracellular domain and implications for its receptor function for recognizing anthrax toxin. PLoS One. 2010 Jun 18;5(6):e11203. PMID:20585457 doi:10.1371/journal.pone.0011203
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