4le9

Publication Abstract from PubMed

In the Src Homology 3 domain (SH3) the RT and n-Src loops form a pocket that accounts for the specificity and affinity in binding of proline rich motifs (PRMs), while the distal and diverging turns play a key role in the folding of the protein. We have solved the structure of a chimeric mutant c-Src-SH3 domain where specific residues at the RT- and n-Src-loops have been replaced by those present in the corresponding Abl-SH3 domain. Crystals of the chimeric protein show a single molecule in the asymmetric unit, which appears in an unfolded-like structure that upon generation of the symmetry related molecules reveals the presence of a domain swapped dimer where both, RT- and n-Src loops, act as hinge loops. In contrast, the fold of the diverging type II beta-turn and the distal loop are well conserved. Our results are the first evidence for the presence of a structured diverging type II beta-turn in an unfolded-like intermediate of the c-Src-SH3 domain, which can be stabilized by interactions from the beta-strands of the same polypeptide chain or from a neighboring one. Futhermore, this crystallographic structure opens a unique opportunity to study the effect of the amino acid sequence of the hinge loops on the 3D domain swapping process of c-Src-SH3.

3D domain swapping in a chimeric c-Src SH3 domain takes place through two hinge loops.,Camara-Artigas A, Martinez-Rodriguez S, Ortiz-Salmeron E, Martin-Garcia JM J Struct Biol. 2014 Apr;186(1):195-203. doi: 10.1016/j.jsb.2014.02.007. Epub 2014, Feb 17. PMID:24556574^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.