The response of internal dynamics to hydrophobic core mutations in the SH3 domain from the Fyn tyrosine kinase

Authors

  • Anthony Mittermaier,

    Corresponding author
    1. Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    • Departments of Biochemistry, Chemistry and Medical Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8; fax: (416) 978-6885.
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  • Lewis E. Kay

    Corresponding author
    1. Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    2. Departments of Medical Genetics and Chemistry, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    • Departments of Biochemistry, Chemistry and Medical Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8; fax: (416) 978-6885.
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Abstract

We have used 15N- and 2H-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.

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