Structural and kinetic characterization of the simplified SH3 domain FP1

TitleStructural and kinetic characterization of the simplified SH3 domain FP1
Publication TypeJournal Article
Year of Publication2003
AuthorsYi, Q., Rajagopal P., Klevit R. E., & Baker D.
JournalProtein science
Volume12
Issue4
Pagination776-83
Date Published2003 Apr
ISSN0961-8368
KeywordsKinetics, Magnetic Resonance Spectroscopy, Mutation, Primary Publication, src Homology Domains
Abstract

The simplified SH3 domain sequence, FP1, obtained in phage display selection experiments has an amino acid composition that is 95% Ile, Lys, Glu, Ala, Gly. Here we use NMR to investigate the tertiary structure of FP1. We find that the overall topology of FP1 resembles that of the src SH3 domain, the hydrogen-deuterium exchange and chemical shift perturbation profiles are similar to those of naturally occurring SH3 domains, and the (15)N relaxation rates are in the range of naturally occurring small proteins. Guided by the structure, we further simplify the FP1 sequence and compare the effects on folding kinetics of point mutations in FP1 and the wild-type src SH3 domain. The results suggest that the folding transition state of FP1 is similar to but somewhat less polarized than that of the wild-type src SH3 domain.

Alternate JournalProtein Sci.
AttachmentSize
yi03A.pdf399.69 KB