The role of water molecules in the binding of class I and II peptides to the SH3 domain of the Fyn tyrosine kinase.
Interactions of proline-rich motifs with SH3 domains are present in signal transduction and other important cell processes. Analysis of structural and thermodynamic data suggest a relevant role of water molecules in these protein-protein interactions. To determine whether or not the SH3 domain of the Fyn tyrosine kinase shows the same behaviour, the crystal structures of its complexes with two high-affinity synthetic peptides, VSL12 and APP12, which are class I and II peptides, respectively, have been solved. In the class I complexes two water molecules were found at the binding interface that were not present in the class II complexes. The structures suggest a role of these water molecules in facilitating conformational changes in the SH3 domain to allow the binding of the class I or II peptides. In the third binding pocket these changes modify the cation-π and salt-bridge interactions that determine the affinity of the binding. Comparison of the water molecules involved in the binding of the peptides with previous reported hydration spots suggests a different pattern for the SH3 domains of the Src tyrosine kinase family.
Department of Chemistry and Physics, University of Almería, Agrifood Campus of International Excellence (ceiA3), Carretera de Sacramento, 04120 Almeria, Spain.
Ana
A
Camara-Artigas
Department of Chemistry and Physics, University of Almería, Agrifood Campus of International Excellence (ceiA3), Carretera de Sacramento, 04120 Almeria, Spain.
Emilia
E
Ortiz-Salmeron
Department of Chemistry and Physics, University of Almería, Agrifood Campus of International Excellence (ceiA3), Carretera de Sacramento, 04120 Almeria, Spain.
Montserrrat
M
Andujar-Sánchez
Department of Chemistry and Physics, University of Almería, Agrifood Campus of International Excellence (ceiA3), Carretera de Sacramento, 04120 Almeria, Spain.
Julio
J
Bacarizo
School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA.
Jose Manuel
JM
Martin-Garcia
D000595:Amino Acid Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D051076:Proto-Oncogene Proteins c-fyn / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics; D014867:Water / Q000737:chemistry* / Q000378:metabolism; D018909:src Homology Domains
D010455:Peptides; D011994:Recombinant Proteins; D014867:Water; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn
Fyn tyrosine kinase; SH3 domain; X-ray crystal structure; proline-rich motifs