The response of internal dynamics to hydrophobic core mutations in the SH3 domain from the Fyn tyrosine kinase.
We have used (15)N- and (2)H-NMR spin relaxation experiments to study the response of backbone and side-chain dynamics when a leucine or valine is substituted for a completely buried phenylalanine residue in the SH3 domain from the Fyn tyrosine kinase. Several residues show differences in the time scales and temperature dependences of internal motions when data for the three proteins are compared. Changes were also observed in the magnitude of dynamics, with the valine, and to a lesser extent leucine mutant, showing enhanced flexibility compared to the wild-type (WT) protein. The motions of many of the same amide and methyl groups are affected by both mutations, identifying a set of loci where dynamics are sensitive to interactions involving the targeted side chain. These results show that contacts within the hydrophobic core affect many aspects of internal mobility throughout the Fyn SH3 domain.
Mittermaier
Anthony
A
Departments of Biochemistry, Chemistry and Medical Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8. tmitter@pound.med.utoronto.ca
Kay
Lewis E
LE
D019943:Amino Acid Substitution; D000818:Animals; D002645:Chickens; D057927:Hydrophobic and Hydrophilic Interactions; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D017434:Protein Structure, Tertiary / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000235:genetics; D051076:Proto-Oncogene Proteins c-fyn; D013696:Temperature
D011518:Proto-Oncogene Proteins; D051076:Proto-Oncogene Proteins c-fyn