2c5d

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{{Seed}}
 
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[[Image:2c5d.png|left|200px]]
 
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==Structure of a minimal Gas6-Axl complex==
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The line below this paragraph, containing "STRUCTURE_2c5d", creates the "Structure Box" on the page.
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<StructureSection load='2c5d' size='340' side='right'caption='[[2c5d]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2c5d]] is a 4 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=2C5D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2C5D FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
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<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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_2c5d| PDB=2c5d | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2c5d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2c5d OCA], [https://pdbe.org/2c5d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2c5d RCSB], [https://www.ebi.ac.uk/pdbsum/2c5d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2c5d ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/UFO_HUMAN UFO_HUMAN] Note=AXL and its ligand GAS6 are highly expressed in thyroid carcinoma tissues, and might thus be involved in thyroid tumorigenesis. Overexpression of AXL and its ligand was also detected in many other cancers such as myeloproliferative disorders, prostatic carcinoma cells, or breast cancer.
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== Function ==
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[https://www.uniprot.org/uniprot/UFO_HUMAN UFO_HUMAN] Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, ALX binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TENC1. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response. In case of filovirus infection, seems to function as a cell entry factor.<ref>PMID:1656220</ref> <ref>PMID:10403904</ref> <ref>PMID:11484958</ref> <ref>PMID:12364394</ref> <ref>PMID:12490074</ref> <ref>PMID:15507525</ref> <ref>PMID:15733062</ref> <ref>PMID:17005688</ref> <ref>PMID:18840707</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c5/2c5d_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2c5d ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Receptor tyrosine kinases of the Axl family are activated by the vitamin K-dependent protein Gas6. Axl signalling plays important roles in cancer, spermatogenesis, immunity, and platelet function. The crystal structure at 3.3 A resolution of a minimal human Gas6/Axl complex reveals an assembly of 2:2 stoichiometry, in which the two immunoglobulin-like domains of the Axl ectodomain are crosslinked by the first laminin G-like domain of Gas6, with no direct Axl/Axl or Gas6/Gas6 contacts. There are two distinct Gas6/Axl contacts of very different size, both featuring interactions between edge beta-strands. Structure-based mutagenesis, protein binding assays and receptor activation experiments demonstrate that both the major and minor Gas6 binding sites are required for productive transmembrane signalling. Gas6-mediated Axl dimerisation is likely to occur in two steps, with a high-affinity 1:1 Gas6/Axl complex forming first. Only the minor Gas6 binding site is highly conserved in the other Axl family receptors, Sky/Tyro3 and Mer. Specificity at the major contact is suggested to result from the segregation of charged and apolar residues to opposite faces of the newly formed beta-sheet.
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===STRUCTURE OF A MINIMAL GAS6-AXL COMPLEX===
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Structural basis for Gas6-Axl signalling.,Sasaki T, Knyazev PG, Clout NJ, Cheburkin Y, Gohring W, Ullrich A, Timpl R, Hohenester E EMBO J. 2006 Jan 11;25(1):80-7. Epub 2005 Dec 15. PMID:16362042<ref>PMID:16362042</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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The line below this paragraph, {{ABSTRACT_PUBMED_16362042}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2c5d" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 16362042 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_16362042}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2C5D is a [[Protein complex]] 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=2C5D OCA].
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==Reference==
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Structural basis for Gas6-Axl signalling., Sasaki T, Knyazev PG, Clout NJ, Cheburkin Y, Gohring W, Ullrich A, Timpl R, Hohenester E, EMBO J. 2006 Jan 11;25(1):80-7. Epub 2005 Dec 15. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16362042 16362042]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Transferase]]
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[[Category: Cheburkin Y]]
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[[Category: Cheburkin, Y.]]
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[[Category: Clout NJ]]
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[[Category: Clout, N J.]]
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[[Category: Goehring W]]
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[[Category: Goehring, W.]]
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[[Category: Hohenester E]]
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[[Category: Hohenester, E.]]
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[[Category: Knyazev PG]]
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[[Category: Knyazev, P G.]]
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[[Category: Sasaki T]]
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[[Category: Sasaki, T.]]
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[[Category: Timpl R]]
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[[Category: Timpl, R.]]
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[[Category: Ullrich A]]
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[[Category: Ullrich, A.]]
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[[Category: Egf-like domain]]
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[[Category: Growth regulation]]
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[[Category: Immunoglobulin-like domain]]
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[[Category: Laminin g-like domain]]
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[[Category: Receptor]]
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[[Category: Receptor tyrosine kinase]]
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[[Category: Vitamin k-dependent protein]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 23:13:58 2008''
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Current revision

Structure of a minimal Gas6-Axl complex

PDB ID 2c5d

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