Linker length dependent binding of a focal adhesion kinase derived peptide to the Src SH3-SH2 domains.
The interaction between a peptide encompassing the SH3 and SH2 binding motifs of focal adhesion kinase (FAK) and the Src SH3-SH2 domains has been investigated with NMR spectroscopy and calorimetry. The binding to both motifs is anti-cooperative. Reduction of the long linker connecting the motifs does not lead to cooperativity. Short linkers that do not allow simultaneous intramolecular binding of the peptide to both motifs cause peptide-mediated dimerisation, even with a linker of only three amino acids. The role of the SH3 binding motif is discussed in view of the independent nature of the SH interactions.
Leiden University, Leiden Institute of Chemistry, Leiden, The Netherlands.
Hanna E
HE
Lindfors
Bharat Somireddy
BS
Venkata
Jan W
JW
Drijfhout
Marcellus
M
Ubbink
D000595:Amino Acid Sequence; D000818:Animals; D002151:Calorimetry; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D018909:src Homology Domains; D019061:src-Family Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D010455:Peptides; D011993:Recombinant Fusion Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases