Long-distance conformational changes in a protein engineered by modulated sequence duplication.
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.
Sagermann
Martin
M
Institute of Molecular Biology, Howard Hughes Medical Institute and Department of Physics, University of Oregon, Eugene, OR 97403-1229, USA.
Gay
Leslie
L
Matthews
Brian W
BW
D001665:Binding Sites; D018360:Crystallography, X-Ray; D005998:Glycine / Q000737:chemistry; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry* / Q000235:genetics*; D016296:Mutagenesis; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics*; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
D010446:Peptide Fragments; D010455:Peptides; C094995:T4 lysozyme (38-51); C019529:polyalanine; D009113:Muramidase; D005998:Glycine