A crystallographic snapshot of tyrosine trans-phosphorylation in action.

Details

Serval ID
serval:BIB_E0465F7B7C88
Type
Article: article from journal or magazin.
Collection
Publications
Title
A crystallographic snapshot of tyrosine trans-phosphorylation in action.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Chen H., Xu C.F., Ma J., Eliseenkova A.V., Li W., Pollock P.M., Pitteloud N., Miller W.T., Neubert T.A., Mohammadi M.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
105
Number
50
Pages
19660-19665
Language
english
Notes
Publication types: Journal Article
Abstract
Tyrosine trans-phosphorylation is a key event in receptor tyrosine kinase signaling, yet, the structural basis for this process has eluded definition. Here, we present the crystal structure of the FGF receptor 2 kinases caught in the act of trans-phosphorylation of Y769, the major C-terminal phosphorylation site. The structure reveals that enzyme- and substrate-acting kinases engage each other through elaborate and specific interactions not only in the immediate vicinity of Y769 and the enzyme active site, but also in regions that are as much of 18 A away from D626, the catalytic base in the enzyme active site. These interactions lead to an unprecedented level of specificity and precision during the trans-phosphorylation on Y769. Time-resolved mass spectrometry analysis supports the observed mechanism of trans-phosphorylation. Our data provide a molecular framework for understanding the mechanism of action of Kallmann syndrome mutations and the order of trans-phosphorylation reactions in FGFRs. We propose that the salient mechanistic features of Y769 trans-phosphorylation are applicable to trans-phosphorylation of the equivalent major phosphorylation sites in many other RTKs.
Keywords
Catalytic Domain, Crystallography, X-Ray, Humans, Kallmann Syndrome/genetics, Mutation, Phosphorylation, Protein Structure, Tertiary, Receptor, Fibroblast Growth Factor, Type 2/chemistry, Receptor, Fibroblast Growth Factor, Type 2/genetics, Tyrosine/chemistry, Tyrosine/genetics
Pubmed
Open Access
Yes
Create date
03/12/2014 15:29
Last modification date
20/08/2019 16:04
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