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2o26

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(New page: 200px<br /><applet load="2o26" size="450" color="white" frame="true" align="right" spinBox="true" caption="2o26, resolution 2.50&Aring;" /> '''Structure of a class...)
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[[Image:2o26.gif|left|200px]]<br /><applet load="2o26" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2o26, resolution 2.50&Aring;" />
 
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'''Structure of a class III RTK signaling assembly'''<br />
 
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==Overview==
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==Structure of a class III RTK signaling assembly==
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Stem cell factor (SCF) binds to and activates the KIT receptor, a class, III receptor tyrosine kinase (RTK), to stimulate diverse processes, including melanogenesis, gametogenesis and hematopoeisis. Dysregulation of, KIT activation is associated with many cancers. We report a 2.5 A crystal, structure of the functional core of SCF bound to the extracellular, ligand-binding domains of KIT. The structure reveals a 'wrapping', SCF-recognition mode by KIT, in which KIT adopts a bent conformation to, facilitate each of its first three immunoglobulin (Ig)-like domains to, interact with SCF. Three surface epitopes on SCF, an extended loop, the B, and C helices, and the N-terminal segment, contact distinct KIT domains, with two of the epitopes undergoing large conformational changes upon, receptor binding. The SCF/KIT complex reveals a unique RTK dimerization, assembly, and a novel recognition mode between four-helix bundle cytokines, and Ig-family receptors. It serves as a framework for understanding the, activation mechanisms of class III RTKs.
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<StructureSection load='2o26' size='340' side='right'caption='[[2o26]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2o26]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O26 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2O26 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]] 2.5&#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=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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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=2o26 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o26 OCA], [https://pdbe.org/2o26 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2o26 RCSB], [https://www.ebi.ac.uk/pdbsum/2o26 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2o26 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SCF_MOUSE SCF_MOUSE] Ligand for the receptor-type protein-tyrosine kinase KIT. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. KITLG/SCF binding can activate several signaling pathways. Promotes phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and subsequent activation of the kinase AKT1. KITLG/SCF and KIT also transmit signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. KITLG/SCF and KIT promote activation of STAT family members STAT1, STAT3 and STAT5. KITLG/SCF and KIT promote activation of PLCG1, leading to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KITLG/SCF acts synergistically with other cytokines, probably interleukins.
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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/o2/2o26_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2o26 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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Stem cell factor (SCF) binds to and activates the KIT receptor, a class III receptor tyrosine kinase (RTK), to stimulate diverse processes including melanogenesis, gametogenesis and hematopoeisis. Dysregulation of KIT activation is associated with many cancers. We report a 2.5 A crystal structure of the functional core of SCF bound to the extracellular ligand-binding domains of KIT. The structure reveals a 'wrapping' SCF-recognition mode by KIT, in which KIT adopts a bent conformation to facilitate each of its first three immunoglobulin (Ig)-like domains to interact with SCF. Three surface epitopes on SCF, an extended loop, the B and C helices, and the N-terminal segment, contact distinct KIT domains, with two of the epitopes undergoing large conformational changes upon receptor binding. The SCF/KIT complex reveals a unique RTK dimerization assembly, and a novel recognition mode between four-helix bundle cytokines and Ig-family receptors. It serves as a framework for understanding the activation mechanisms of class III RTKs.
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==About this Structure==
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Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases.,Liu H, Chen X, Focia PJ, He X EMBO J. 2007 Feb 7;26(3):891-901. Epub 2007 Jan 25. PMID:17255936<ref>PMID:17255936</ref>
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2O26 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2O26 OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases., Liu H, Chen X, Focia PJ, He X, EMBO J. 2007 Feb 7;26(3):891-901. Epub 2007 Jan 25. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17255936 17255936]
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</div>
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[[Category: Mus musculus]]
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<div class="pdbe-citations 2o26" style="background-color:#fffaf0;"></div>
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[[Category: Protein complex]]
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[[Category: Receptor protein-tyrosine kinase]]
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[[Category: Chen, X.]]
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[[Category: Focia, P.J.]]
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[[Category: He, X.]]
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[[Category: Liu, H.]]
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[[Category: 4-helix bundle]]
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[[Category: class iii]]
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[[Category: cytokine]]
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[[Category: growth factor]]
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[[Category: receptor tyrosine kinase]]
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[[Category: receptor/ligand complex]]
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[[Category: stem cell factor]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 13:01:56 2007''
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==See Also==
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*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Mus musculus]]
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[[Category: Chen X]]
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[[Category: Focia PJ]]
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[[Category: He X]]
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[[Category: Liu H]]

Current revision

Structure of a class III RTK signaling assembly

PDB ID 2o26

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