Long-distance conformational changes in a protein engineered by modulated sequence duplication

Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9191-5. doi: 10.1073/pnas.1633549100. Epub 2003 Jul 17.

Abstract

There are few, if any, known instances in which a biological signal is transmitted via a large conformational change through the body of a protein. We describe here a mutant of T4 lysozyme that was engineered to permit structural change at a distance. The design uses a tandem sequence repeat that makes it possible to transmit large-scale structural changes from one end of an alpha-helix to the other over a distance of 17-25 A. The method should be of general applicability and may make it possible to introduce a mutation at one site in a protein that will induce large-scale changes in the structure at a spatially remote site.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Glycine / chemistry
  • Models, Molecular
  • Muramidase / chemistry*
  • Muramidase / genetics*
  • Mutagenesis*
  • Mutation
  • Peptide Fragments / chemistry*
  • Peptide Fragments / genetics*
  • Peptides / chemistry
  • Protein Conformation
  • Protein Structure, Tertiary

Substances

  • Peptide Fragments
  • Peptides
  • T4 lysozyme (38-51)
  • polyalanine
  • Muramidase
  • Glycine

Associated data

  • PDB/1OYU