Fast and faster: a designed variant of the B-domain of protein A folds in 3 microsec.


Journal Article

We have introduced the mutation glycine 29 to alanine, designed to increase the rate of protein folding, into the B-domain of protein A (BdpA). From NMR lineshape analysis, we find the G29A mutation increases the folding rate constant by threefold; the folding time is 3 microsec. Although wild-type BdpA folds extremely fast, simple-point mutations can still speed up the folding; thus, the folding rate is not evolutionarily maximized. The short folding time of G29A BdpA (the shortest time yet reported) makes it an attractive candidate for an all-atom molecular dynamics simulation that could potentially show a complete folding reaction starting from an extended chain. We also constructed a fluorescent variant of BdpA by mutating phenylalanine 13 to tryptophan, allowing fluorescence-based time-resolved temperature-jump measurements. Temperature jumps and NMR complement each other, and give a very complete picture of the folding kinetics.

Full Text

Duke Authors

Cited Authors

  • Arora, P; Oas, TG; Myers, JK

Published Date

  • April 2004

Published In

Volume / Issue

  • 13 / 4

Start / End Page

  • 847 - 853

PubMed ID

  • 15044721

Pubmed Central ID

  • 15044721

International Standard Serial Number (ISSN)

  • 0961-8368

Digital Object Identifier (DOI)

  • 10.1110/ps.03541304


  • eng

Conference Location

  • United States