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Crystallographic structure of the SH3 domain of the human c‐Yes tyrosine kinase: Loop flexibility and amyloid aggregation
Author(s) -
Martín-García José M.,
Luque Irene,
Mateo Pedro L.,
Ruiz-Sanz Javier,
Cámara-Artigas Ana
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.03.059
Subject(s) - sh3 domain , proto oncogene tyrosine protein kinase src , tyrosine kinase , hydrogen bond , kinase , chemistry , tyrosine , receptor tyrosine kinase , biophysics , crystallography , computational biology , biochemistry , biology , signal transduction , molecule , organic chemistry
SH3 domains from the Src family of tyrosine kinases represent an interesting example of the delicate balance between promiscuity and specificity characteristic of proline‐rich ligand recognition by SH3 domains. The development of inhibitors of therapeutic potential requires a good understanding of the molecular determinants of binding affinity and specificity and relies on the availability of high quality structural information. Here, we present the first high‐resolution crystal structure of the SH3 domain of the c‐Yes oncogen. Comparison with other SH3 domains from the Src family revealed significant deviations in the loop regions. In particular, the n‐Src loop, highly flexible and partially disordered, is stabilized in an unusual conformation by the establishment of several intramolecular hydrogen bonds. Additionally, we present here the first report of amyloid aggregation by an SH3 domain from the Src family.