title: 3D domain swapping in a chimeric c-Src SH3 domain takes place through two hinge loops.
abstract: 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have solved the structure of a chimeric mutant c-Src-SH3 domain where specific residues at the RT- and n-Src-loops have been replaced by those present in the corresponding Abl-SH3 domain.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 β-turn and the distal loop are well conserved. Our results are the first evidence for the presence of a structured diverging type II β-turn in an unfolded-like intermediate of the c-Src-SH3 domain, which can be stabilized by interactions from the β-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.
authors.affiliation: Department of Chemistry and Physics, Research Centre for Agricultural and Food Biotechnology (BITAL), University of Almería, Agrifood Campus of International Excellence (ceiA3), Carretera de Sacramento, Almería 04120, Spain. Electronic address: acamara@ual.es.
authors.forename: Ana
authors.initials: A
authors.lastname: Cámara-Artigas
authors.affiliation: Department of Chemistry and Physics, Research Centre for Agricultural and Food Biotechnology (BITAL), University of Almería, Agrifood Campus of International Excellence (ceiA3), Carretera de Sacramento, Almería 04120, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Martínez-Rodríguez
authors.affiliation: Department of Chemistry and Physics, Research Centre for Agricultural and Food Biotechnology (BITAL), University of Almería, Agrifood Campus of International Excellence (ceiA3), Carretera de Sacramento, Almería 04120, Spain.
authors.forename: Emilia
authors.initials: E
authors.lastname: Ortiz-Salmerón
authors.affiliation: Department of Chemistry and Physics, Research Centre for Agricultural and Food Biotechnology (BITAL), University of Almería, Agrifood Campus of International Excellence (ceiA3), Carretera de Sacramento, Almería 04120, Spain; Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287, United States.
authors.forename: José M
authors.initials: JM
authors.lastname: Martín-García
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins / Q000737:chemistry*; D002645:Chickens; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D018909:src Homology Domains; D019061:src-Family Kinases / Q000737:chemistry*
chemical_list: D030161:Avian Proteins; D011993:Recombinant Fusion Proteins; D019061:src-Family Kinases
keywords: 3D domain swapping; Abl tyrosine kinase; SH3 domain; c-Src tyrosine kinase