English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/55974
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

Conformational rearrangements upon Syk auto-phosphorylation

AuthorsArias-Palomo, Ernesto ; Recuero-Checa, María Ángeles ; Bustelo, Xosé R. ; Llorca, Óscar
Issue DateAug-2009
PublisherElsevier
CitationBBA - Proteins and Proteomics 1794(8): 1211-1217 (2009)
AbstractSyk is a cytoplasmic tyrosine kinase that is activated after recruitment to immune receptors, triggering the phopshorylation of downstream targets. The kinase activity of Syk is controlled by an auto-inhibited conformation consisting of a regulatory region that contains two N-terminal Src homology 2 (SH2) domains inhibiting the catalytic activity of the kinase domain located at the C-terminus. The atomic structure of the related Zap-70 kinase and an electron microscopy (EM) model of Syk have revealed the structural mechanism of this auto-inhibition based on the formation of a compact conformation sustained by interactions between the regulatory and catalytic domains. On the other hand, the structural basis of Syk activation is not fully understood due to the lack of a 3D structure of full-length Syk in an active conformation. Here, we have used single-particle electron microscopy to analyse the conformational changes taking place in an activated form of Syk induced by auto-phosphorylation. The conformation of phosphorylated Syk is reminiscent of the compact structure of the inhibited protein but significant conformational changes are observed in the regulatory region. These rearrangements could be sufficient to disrupt the inhibitory interactions, contributing to Syk activation. These results suggest that the regulation of the activation of Syk might be modulated by subtle changes in the positioning of the regulatory domains rather than a full opening mechanism as proposed for the Src kinases.
Description7 páginas, 3 figuras.
Publisher version (URL)http://dx.doi.org/10.1016/j.bbapap.2009.04.010
URIhttp://hdl.handle.net/10261/55974
DOI10.1016/j.bbapap.2009.04.010
ISSN1570-9639
Appears in Collections:(IBMCC) Artículos
(CIB) Artículos
Files in This Item:
File Description SizeFormat 
restringido.pdf21,67 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.