3bun: Difference between revisions

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Revision as of 20:01, 20 March 2008

File:3bun.jpg

, resolution 2.000Å

Gene:

CBL, CBL2, RNF55 (Homo sapiens)

Coordinates:

save as pdb, mmCIF, xml

Crystal structure of c-Cbl-TKB domain complexed with its binding motif in Sprouty4

OverviewOverview

The c-Cbl tyrosine kinase binding domain (Cbl-TKB), essentially an 'embedded' SH2 domain, has a critical role in targeting proteins for ubiquitination. To address how this domain can bind to disparate recognition mofits and to determine whether this results in variations in substrate-binding affinity, we compared crystal structures of the Cbl-TKB domain complexed with phosphorylated peptides of Sprouty2, Sprouty4, epidermal growth factor receptor, Syk, and c-Met receptors and validated the binding with point-mutational analyses using full-length proteins. An obligatory, intrapeptidyl H-bond between the phosphotyrosine and the conserved asparagine or adjacent arginine is essential for binding and orientates the peptide into a positively charged pocket on c-Cbl. Surprisingly, c-Met bound to Cbl in the reverse direction, which is unprecedented for SH2 domain binding. The necessity of this intrapeptidyl H-bond was confirmed with isothermal titration calorimetry experiments that also showed Sprouty2 to have the highest binding affinity to c-Cbl; this may enable the selective sequestration of c-Cbl from other target proteins.

About this StructureAbout this Structure

3BUN is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates., Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J, EMBO J. 2008 Feb 14;. PMID:18273061

Page seeded by OCA on Thu Mar 20 19:01:22 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:3bun.jpg|left|200px]]<br /><applet load="3bun" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:3bun.jpg|left|200px]]
-caption="3bun, resolution 2.000&Aring;" />
-'''Crystal structure of c-Cbl-TKB domain complexed with its binding motif in Sprouty4'''<br />
+ {{Structure
+|PDB= 3bun |SIZE=350|CAPTION= <scene name='initialview01'>3bun</scene>, resolution 2.000&Aring;
+|SITE=
+|LIGAND=
+|ACTIVITY=
+|GENE= CBL, CBL2, RNF55 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+}}
+'''Crystal structure of c-Cbl-TKB domain complexed with its binding motif in Sprouty4'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-BUN is a [http://en.wikipedia.org/wiki/Protein_complex 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=3BUN OCA].
+BUN 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=3BUN OCA].
 ==Reference==
-Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates., Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J, EMBO J. 2008 Feb 14;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18273061 18273061]
+Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates., Ng C, Jackson RA, Buschdorf JP, Sun Q, Guy GR, Sivaraman J, EMBO J. 2008 Feb 14;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18273061 18273061]
 [[Category: Homo sapiens]]
 [[Category: Protein complex]]
@@ Line 38: / Line 47: @@
 [[Category: zinc-finger]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 27 07:59:51 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 19:01:22 2008''