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- | {{Seed}} | |
- | [[Image:3k6s.jpg|left|200px]] | |
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- | <!-- | + | ==Structure of integrin alphaXbeta2 ectodomain== |
- | The line below this paragraph, containing "STRUCTURE_3k6s", creates the "Structure Box" on the page.
| + | <StructureSection load='3k6s' size='340' side='right'caption='[[3k6s]], [[Resolution|resolution]] 3.50Å' scene=''> |
- | You may change the PDB parameter (which sets the PDB file loaded into the applet) | + | == Structural highlights == |
- | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[3k6s]] is a 8 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=3K6S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3K6S FirstGlance]. <br> |
- | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.5Å</td></tr> |
- | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
- | {{STRUCTURE_3k6s| PDB=3k6s | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3k6s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3k6s OCA], [https://pdbe.org/3k6s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3k6s RCSB], [https://www.ebi.ac.uk/pdbsum/3k6s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3k6s ProSAT]</span></td></tr> |
| + | </table> |
| + | == Disease == |
| + | [https://www.uniprot.org/uniprot/ITB2_HUMAN ITB2_HUMAN] Defects in ITGB2 are the cause of leukocyte adhesion deficiency type 1 (LAD1) [MIM:[https://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 == |
| + | [https://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/k6/3k6s_consurf.spt"</scriptWhenChecked> |
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=3k6s ConSurf]. |
| + | <div style="clear:both"></div> |
| + | <div style="background-color:#fffaf0;"> |
| + | == Publication Abstract from PubMed == |
| + | We report the structure of an integrin with an alphaI domain, alpha(X)beta(2), the complement receptor type 4. It was earlier expected that a fixed orientation between the alphaI domain and the beta-propeller domain in which it is inserted would be required for allosteric signal transmission. However, the alphaI domain is highly flexible, enabling two betaI domain conformational states to couple to three alphaI domain states, and greater accessibility for ligand recognition. Although alpha(X)beta(2) is bent similarly to integrins that lack alphaI domains, the terminal domains of the alpha- and beta-legs, calf-2 and beta-tail, are oriented differently than in alphaI-less integrins. Linkers extending to the transmembrane domains are unstructured. Previous mutations in the beta(2)-tail domain support the importance of extension, rather than a deadbolt, in integrin activation. The locations of further activating mutations and antibody epitopes show the critical role of extension, and conversion from the closed to the open headpiece conformation, in integrin activation. Differences among 10 molecules in crystal lattices provide unprecedented information on interdomain flexibility important for modelling integrin extension and activation. |
| | | |
- | ===Structure of integrin alphaXbeta2 ectodomain===
| + | Structure of an integrin with an alphaI domain, complement receptor type 4.,Xie C, Zhu J, Chen X, Mi L, Nishida N, Springer TA EMBO J. 2010 Feb 3;29(3):666-79. Epub 2009 Dec 24. PMID:20033057<ref>PMID:20033057</ref> |
| | | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| + | </div> |
| + | <div class="pdbe-citations 3k6s" style="background-color:#fffaf0;"></div> |
| | | |
- | ==About this Structure== | + | ==See Also== |
- | 3K6S is a 8 chains structure of sequences 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=3K6S OCA].
| + | *[[Integrin 3D structures|Integrin 3D structures]] |
| + | == References == |
| + | <references/> |
| + | __TOC__ |
| + | </StructureSection> |
| [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
- | [[Category: Chen, X.]] | + | [[Category: Large Structures]] |
- | [[Category: Mi, L.]] | + | [[Category: Chen X]] |
- | [[Category: Nishida, N.]] | + | [[Category: Mi L]] |
- | [[Category: Springer, T A.]] | + | [[Category: Nishida N]] |
- | [[Category: Xie, C.]] | + | [[Category: Springer TA]] |
- | [[Category: Zhu, J.]] | + | [[Category: Xie C]] |
- | [[Category: Adhesion molecule]]
| + | [[Category: Zhu J]] |
- | [[Category: Calcium]]
| + | |
- | [[Category: Cell adhesion]]
| + | |
- | [[Category: Cell receptor]]
| + | |
- | [[Category: Disease mutation]]
| + | |
- | [[Category: Disulfide bond]]
| + | |
- | [[Category: Glycoprotein]]
| + | |
- | [[Category: Hetero dimer]]
| + | |
- | [[Category: Integrin]]
| + | |
- | [[Category: Magnesium]]
| + | |
- | [[Category: Membrane]]
| + | |
- | [[Category: Phosphoprotein]]
| + | |
- | [[Category: Polymorphism]]
| + | |
- | [[Category: Pyrrolidone carboxylic acid]]
| + | |
- | [[Category: Receptor]]
| + | |
- | [[Category: Transmembrane]]
| + | |
- | | + | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 13 14:32:25 2010''
| + | |
| Structural highlights
Disease
ITB2_HUMAN Defects in ITGB2 are the cause of leukocyte adhesion deficiency type 1 (LAD1) [MIM:116920. LAD1 patients have recurrent bacterial infections and their leukocytes are deficient in a wide range of adhesion-dependent functions.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11]
Function
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.[12]
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
We report the structure of an integrin with an alphaI domain, alpha(X)beta(2), the complement receptor type 4. It was earlier expected that a fixed orientation between the alphaI domain and the beta-propeller domain in which it is inserted would be required for allosteric signal transmission. However, the alphaI domain is highly flexible, enabling two betaI domain conformational states to couple to three alphaI domain states, and greater accessibility for ligand recognition. Although alpha(X)beta(2) is bent similarly to integrins that lack alphaI domains, the terminal domains of the alpha- and beta-legs, calf-2 and beta-tail, are oriented differently than in alphaI-less integrins. Linkers extending to the transmembrane domains are unstructured. Previous mutations in the beta(2)-tail domain support the importance of extension, rather than a deadbolt, in integrin activation. The locations of further activating mutations and antibody epitopes show the critical role of extension, and conversion from the closed to the open headpiece conformation, in integrin activation. Differences among 10 molecules in crystal lattices provide unprecedented information on interdomain flexibility important for modelling integrin extension and activation.
Structure of an integrin with an alphaI domain, complement receptor type 4.,Xie C, Zhu J, Chen X, Mi L, Nishida N, Springer TA EMBO J. 2010 Feb 3;29(3):666-79. Epub 2009 Dec 24. PMID:20033057[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ohashi Y, Yambe T, Tsuchiya S, Kikuchi H, Konno T. Familial genetic defect in a case of leukocyte adhesion deficiency. Hum Mutat. 1993;2(6):458-67. PMID:7509236 doi:http://dx.doi.org/10.1002/humu.1380020606
- ↑ Nelson C, Rabb H, Arnaout MA. Genetic cause of leukocyte adhesion molecule deficiency. Abnormal splicing and a missense mutation in a conserved region of CD18 impair cell surface expression of beta 2 integrins. J Biol Chem. 1992 Feb 15;267(5):3351-7. PMID:1346613
- ↑ Arnaout MA, Dana N, Gupta SK, Tenen DG, Fathallah DM. Point mutations impairing cell surface expression of the common beta subunit (CD18) in a patient with leukocyte adhesion molecule (Leu-CAM) deficiency. J Clin Invest. 1990 Mar;85(3):977-81. PMID:1968911 doi:http://dx.doi.org/10.1172/JCI114529
- ↑ Wardlaw AJ, Hibbs ML, Stacker SA, Springer TA. Distinct mutations in two patients with leukocyte adhesion deficiency and their functional correlates. J Exp Med. 1990 Jul 1;172(1):335-45. PMID:1694220
- ↑ Matsuura S, Kishi F, Tsukahara M, Nunoi H, Matsuda I, Kobayashi K, Kajii T. Leukocyte adhesion deficiency: identification of novel mutations in two Japanese patients with a severe form. Biochem Biophys Res Commun. 1992 May 15;184(3):1460-7. PMID:1590804
- ↑ Corbi AL, Vara A, Ursa A, Garcia Rodriguez MC, Fontan G, Sanchez-Madrid F. Molecular basis for a severe case of leukocyte adhesion deficiency. Eur J Immunol. 1992 Jul;22(7):1877-81. PMID:1352501 doi:http://dx.doi.org/10.1002/eji.1830220730
- ↑ Back AL, Kwok WW, Hickstein DD. Identification of two molecular defects in a child with leukocyte adherence deficiency. J Biol Chem. 1992 Mar 15;267(8):5482-7. PMID:1347532
- ↑ Back AL, Kerkering M, Baker D, Bauer TR, Embree LJ, Hickstein DD. A point mutation associated with leukocyte adhesion deficiency type 1 of moderate severity. Biochem Biophys Res Commun. 1993 Jun 30;193(3):912-8. PMID:7686755 doi:http://dx.doi.org/10.1006/bbrc.1993.1712
- ↑ Hogg N, Stewart MP, Scarth SL, Newton R, Shaw JM, Law SK, Klein N. A novel leukocyte adhesion deficiency caused by expressed but nonfunctional beta2 integrins Mac-1 and LFA-1. J Clin Invest. 1999 Jan;103(1):97-106. PMID:9884339 doi:10.1172/JCI3312
- ↑ Li L, Jin YY, Cao RM, Chen TX. A novel point mutation in CD18 causing leukocyte adhesion deficiency in a Chinese patient. Chin Med J (Engl). 2010 May 20;123(10):1278-82. PMID:20529581
- ↑ Parvaneh N, Mamishi S, Rezaei A, Rezaei N, Tamizifar B, Parvaneh L, Sherkat R, Ghalehbaghi B, Kashef S, Chavoshzadeh Z, Isaeian A, Ashrafi F, Aghamohammadi A. Characterization of 11 new cases of leukocyte adhesion deficiency type 1 with seven novel mutations in the ITGB2 gene. J Clin Immunol. 2010 Sep;30(5):756-60. doi: 10.1007/s10875-010-9433-2. Epub 2010 , Jun 12. PMID:20549317 doi:10.1007/s10875-010-9433-2
- ↑ Xu J, Gao XP, Ramchandran R, Zhao YY, Vogel SM, Malik AB. Nonmuscle myosin light-chain kinase mediates neutrophil transmigration in sepsis-induced lung inflammation by activating beta2 integrins. Nat Immunol. 2008 Aug;9(8):880-6. doi: 10.1038/ni.1628. Epub 2008 Jun 29. PMID:18587400 doi:10.1038/ni.1628
- ↑ Xie C, Zhu J, Chen X, Mi L, Nishida N, Springer TA. Structure of an integrin with an alphaI domain, complement receptor type 4. EMBO J. 2010 Feb 3;29(3):666-79. Epub 2009 Dec 24. PMID:20033057 doi:10.1038/emboj.2009.367
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