2ec8: Difference between revisions

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{{Seed}}
[[Image:2ec8.png|left|200px]]


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==Crystal structure of the exctracellular domain of the receptor tyrosine kinase, Kit==
The line below this paragraph, containing "STRUCTURE_2ec8", creates the "Structure Box" on the page.
<StructureSection load='2ec8' size='340' side='right'caption='[[2ec8]], [[Resolution|resolution]] 3.00&Aring;' 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'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EC8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2EC8 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&#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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
{{STRUCTURE_2ec8|  PDB=2ec8  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ec8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ec8 OCA], [https://pdbe.org/2ec8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ec8 RCSB], [https://www.ebi.ac.uk/pdbsum/2ec8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ec8 ProSAT]</span></td></tr>
</table>
== 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/ec/2ec8_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=2ec8 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Stem Cell Factor (SCF) initiates its multiple cellular responses by binding to the ectodomain of KIT, resulting in tyrosine kinase activation. We describe the crystal structure of the entire ectodomain of KIT before and after SCF stimulation. The structures show that KIT dimerization is driven by SCF binding whose sole role is to bring two KIT molecules together. Receptor dimerization is followed by conformational changes that enable lateral interactions between membrane proximal Ig-like domains D4 and D5 of two KIT molecules. Experiments with cultured cells show that KIT activation is compromised by point mutations in amino acids critical for D4-D4 interaction. Moreover, a variety of oncogenic mutations are mapped to the D5-D5 interface. Since key hallmarks of KIT structures, ligand-induced receptor dimerization, and the critical residues in the D4-D4 interface, are conserved in other receptors, the mechanism of KIT stimulation unveiled in this report may apply for other receptor activation.


===Crystal structure of the exctracellular domain of the receptor tyrosine kinase, Kit===
Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor.,Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J Cell. 2007 Jul 27;130(2):323-34. PMID:17662946<ref>PMID:17662946</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2ec8" style="background-color:#fffaf0;"></div>


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==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_17662946}}, adds the Publication Abstract to the page
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
(as it appears on PubMed at http://www.pubmed.gov), where 17662946 is the PubMed ID number.
== References ==
-->
<references/>
{{ABSTRACT_PUBMED_17662946}}
__TOC__
 
</StructureSection>
==Disease==
[[Category: Large Structures]]
Known disease associated with this structure: Gastrointestinal stromal tumor, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]], Germ cell tumors OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]], Leukemia, acute myeloid OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]], Mast cell leukemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]], Mastocytosis with associated hematologic disorder OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]], Piebaldism OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]]
[[Category: Lax I]]
 
[[Category: Mandiyan V]]
==About this Structure==
[[Category: Opatowsky Y]]
2EC8 is a [[Single protein]] structure of 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=2EC8 OCA].
[[Category: Schlessinger J]]
 
[[Category: Yuzawa S]]
==Reference==
[[Category: Zhang Z]]
Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor., Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J, Cell. 2007 Jul 27;130(2):323-34. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17662946 17662946]
[[Category: Homo sapiens]]
[[Category: Receptor protein-tyrosine kinase]]
[[Category: Single protein]]
[[Category: Lax, I.]]
[[Category: Mandiyan, V.]]
[[Category: Opatowsky, Y.]]
[[Category: Schlessinger, J.]]
[[Category: Yuzawa, S.]]
[[Category: Zhang, Z.]]
[[Category: Dimerization]]
[[Category: Glycoprotein]]
[[Category: Growth factor cytokine]]
[[Category: Receptor tyrosine kinase]]
[[Category: Transferase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 10:20:55 2008''

Latest revision as of 08:11, 17 October 2024

Crystal structure of the exctracellular domain of the receptor tyrosine kinase, KitCrystal structure of the exctracellular domain of the receptor tyrosine kinase, Kit

Structural highlights

Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

Stem Cell Factor (SCF) initiates its multiple cellular responses by binding to the ectodomain of KIT, resulting in tyrosine kinase activation. We describe the crystal structure of the entire ectodomain of KIT before and after SCF stimulation. The structures show that KIT dimerization is driven by SCF binding whose sole role is to bring two KIT molecules together. Receptor dimerization is followed by conformational changes that enable lateral interactions between membrane proximal Ig-like domains D4 and D5 of two KIT molecules. Experiments with cultured cells show that KIT activation is compromised by point mutations in amino acids critical for D4-D4 interaction. Moreover, a variety of oncogenic mutations are mapped to the D5-D5 interface. Since key hallmarks of KIT structures, ligand-induced receptor dimerization, and the critical residues in the D4-D4 interface, are conserved in other receptors, the mechanism of KIT stimulation unveiled in this report may apply for other receptor activation.

Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor.,Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J Cell. 2007 Jul 27;130(2):323-34. PMID:17662946[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J. Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor. Cell. 2007 Jul 27;130(2):323-34. PMID:17662946 doi:http://dx.doi.org/10.1016/j.cell.2007.05.055

2ec8, resolution 3.00Å

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