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| - | [[Image:1qly.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1qly| PDB=1qly | SCENE= }} | | {{STRUCTURE_1qly| PDB=1qly | SCENE= }} |
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| - | '''NMR STUDY OF THE SH3 DOMAIN FROM BRUTON'S TYROSINE KINASE, 20 STRUCTURES'''
| + | ===NMR STUDY OF THE SH3 DOMAIN FROM BRUTON'S TYROSINE KINASE, 20 STRUCTURES=== |
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| - | ==Overview==
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| - | X-linked agammaglobulinemia (XLA), an inherited disease, is caused by mutations in the Bruton's tyrosine kinase (BTK). The absence of functional BTK leads to failure of B cell differentiation which incapacitates antibody production in XLA patients leading to, sometimes lethal, bacterial infections. Point mutation in the BTK gene that leads to deletion of C-terminal 14 aa residues of BTK SH3 domain was found in one patient family. To understand the role of BTK in B cell development, we have determined the solution structure of BTK SH3 domain complexed with a proline-rich peptide from the protein product of c-cbl protooncogene (p120cbl). Like other SH3 domains, BTK SH3 domain consists of five beta-strands packed in two beta-sheets forming a beta-barrel-like structure. The rmsd calculated from the averaged coordinates for the BTK SH3 domain residues 218-271 and the p120cbl peptide residues 6-12 of the complex was 0.87 A (+/-0.16 A) for the backbone heavy atoms (N, C, and Calpha) and 1.64 A (+/-0.16 A) for all heavy atoms. Based on chemical shift changes and inter-molecular NOEs, we have found that the residues located in the RT loop, n-Src loop and helix-like loop between beta4 and beta5 of BTK SH3 domain are involved in ligand binding. We have also determined that the proline-rich peptide from p120cbl binds to BTK SH3 domain in a class I orientation. These results correlate well with our earlier observation that the truncated BTK SH3 domain (deletion of beta4, beta5 and the helix-like loop) exhibits weaker affinity for the p120cbl peptide. It is likely that the truncated SH3 domain fails to present to the ligand the crucial residues in the correct context and hence the weaker binding. These results delineate the importance of the C-terminus in the binding of SH3 domains and also indicate that improper folding and the altered binding behavior of mutant BTK SH3 domain likely lead to XLA.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10826882}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10826882 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10826882}} |
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| | ==About this Structure== | | ==About this Structure== |
| - | 1QLY 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=1QLY OCA]. | + | 1QLY is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QLY OCA]. |
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| | ==Reference== | | ==Reference== |
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| | [[Category: Transferase]] | | [[Category: Transferase]] |
| | [[Category: Tyrosine-protein kinase]] | | [[Category: Tyrosine-protein kinase]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 06:25:55 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 00:35:51 2008'' |
Revision as of 21:35, 28 July 2008
Template:STRUCTURE 1qly
NMR STUDY OF THE SH3 DOMAIN FROM BRUTON'S TYROSINE KINASE, 20 STRUCTURES
Template:ABSTRACT PUBMED 10826882
About this Structure
1QLY is a Single protein structure of sequence from Homo sapiens. Full experimental information is available from OCA.
Reference
Solution structure of the human BTK SH3 domain complexed with a proline-rich peptide from p120cbl., Tzeng SR, Lou YC, Pai MT, Jain ML, Cheng JW, J Biomol NMR. 2000 Apr;16(4):303-12. PMID:10826882
Page seeded by OCA on Tue Jul 29 00:35:51 2008
