2p28
From Proteopedia
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| - | + | ==Structure of the PHE2 and PHE3 fragments of the integrin beta2 subunit== | |
| - | === | + | <StructureSection load='2p28' size='340' side='right' caption='[[2p28]], [[Resolution|resolution]] 2.20Å' scene=''> |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[2p28]] is a 2 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=2P28 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2P28 FirstGlance]. <br> | ||
| + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene><br> | ||
| + | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2p26|2p26]]</td></tr> | ||
| + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p28 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p28 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2p28 RCSB], [http://www.ebi.ac.uk/pdbsum/2p28 PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/ITB2_HUMAN ITB2_HUMAN]] Defects in ITGB2 are the cause of leukocyte adhesion deficiency type 1 (LAD1) [MIM:[http://omim.org/entry/116920 116920]]. LAD1 patients have recurrent bacterial infections and their leukocytes are deficient in a wide range of adhesion-dependent functions.<ref>PMID:7509236</ref> <ref>PMID:1346613</ref> <ref>PMID:1968911</ref> <ref>PMID:1694220</ref> <ref>PMID:1590804</ref> <ref>PMID:1352501</ref> <ref>PMID:1347532</ref> <ref>PMID:7686755</ref> <ref>PMID:9884339</ref> <ref>PMID:20529581</ref> <ref>PMID:20549317</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/ITB2_HUMAN ITB2_HUMAN]] Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrins alpha-M/beta-2 and alpha-X/beta-2 are receptors for the iC3b fragment of the third complement component and for fibrinogen. Integrin alpha-X/beta-2 recognizes the sequence G-P-R in fibrinogen alpha-chain. Integrin alpha-M/beta-2 recognizes P1 and P2 peptides of fibrinogen gamma chain. Integrin alpha-M/beta-2 is also a receptor for factor X. Integrin alpha-D/beta-2 is a receptor for ICAM3 and VCAM1. Triggers neutrophil transmigration during lung injury through PTK2B/PYK2-mediated activation.<ref>PMID:18587400</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/p2/2p28_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/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Integrins mediate cell adhesion in response to activation signals that trigger conformational changes within their ectodomain. It is thought that a compact bent conformation of the molecule represents its physiological low affinity state and extended conformations its active state. We have determined the structure of two integrin fragments of the beta2 subunit. The first structure, consisting of the plexin-semaphorin-integrin domain, hybrid, integrin-epidermal growth factor 1 (I-EGF1), and I-EGF2 domains (PHE2), showed an L-shaped conformation with the bend located between the I-EGF1 and I-EGF2 domains. The second structure, which includes, in addition, the I-EGF3 domain, showed an extended conformation. The major reorientation of I-EGF2 with respect to the other domains in the two structures is accompanied by a change of torsion angle of the disulfide bond between Cys(461)-Cys(492) by 180 degrees and the conversion of a short alpha-helix (residues Ser(468)-Cys(475)) into a flexible coil. Based on the PHE2 structure, we introduced a disulfide bond between the plexin-semaphorin-integrin domain and I-EGF2 domains in the beta2 subunit. The resultant alphaLbeta2 integrin (leukocyte function-associated antigen-1) variant was locked in a bent state and could not be detected with the monoclonal antibody KIM127 in Mg(2+)/EGTA. However, it retained the binding activity to ICAM-1. These results provide a structural hypothesis for our understanding of the transition between the resting and active states of leukocyte function-associated antigen-1. | ||
| - | + | A structural hypothesis for the transition between bent and extended conformations of the leukocyte beta2 integrins.,Shi M, Foo SY, Tan SM, Mitchell EP, Law SK, Lescar J J Biol Chem. 2007 Oct 12;282(41):30198-206. Epub 2007 Aug 1. PMID:17673459<ref>PMID:17673459</ref> | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Integrin|Integrin]] | *[[Integrin|Integrin]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Foo, S Y.]] | [[Category: Foo, S Y.]] | ||
Revision as of 19:24, 30 September 2014
Structure of the PHE2 and PHE3 fragments of the integrin beta2 subunit
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