2e9w: Difference between revisions
New page: left|200px<br /> <applet load="2e9w" size="450" color="white" frame="true" align="right" spinBox="true" caption="2e9w, resolution 3.50Å" /> '''Crystal structure o... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2e9w. | [[Image:2e9w.jpg|left|200px]]<br /><applet load="2e9w" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="2e9w" size=" | |||
caption="2e9w, resolution 3.50Å" /> | caption="2e9w, resolution 3.50Å" /> | ||
'''Crystal structure of the extracellular domain of Kit in complex with stem cell factor (SCF)'''<br /> | '''Crystal structure of the extracellular domain of Kit in complex with stem cell factor (SCF)'''<br /> | ||
| Line 6: | Line 5: | ||
==Overview== | ==Overview== | ||
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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
2E9W is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG as [http://en.wikipedia.org/wiki/ligand ligand]. 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:// | 2E9W is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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://oca.weizmann.ac.il/oca-bin/ocashort?id=2E9W OCA]. | ||
==Reference== | ==Reference== | ||
| Line 31: | Line 27: | ||
[[Category: transferase/hormone complex]] | [[Category: transferase/hormone complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:15:12 2008'' | ||
