The duplication of an eight-residue helical stretch in Staphylococcal nuclease is not helical: a model for evolutionary change.
A common method of evolutionary change is gene duplication, followed by other events that lead to new function, decoration of folds, oligomerization, or other changes. As part of a study on the potential for evolutionary change created by duplicated sequences, we have carried out a crystallographic study on a mutant of Staphylococcal nuclease in which residues 55-62 have been duplicated in a wild-type variant termed PHS. In the parental protein (PHS) these residues form the first two turns of a helix running from residue 54 to 68 (hereafter designated as helix I). The crystal structure of the mutant is very similar to that of the parental, with helix I being unaltered. The duplicated residues are accommodated by expanding an existing loop N-terminal to helix I. In addition, circular dichroism (CD) studies have been carried out on a parental peptide containing helix I with six flanking residues at each terminus (residues 48-74) and on the same peptide expanded by the duplication, as a function of 2,2,2-trifluoroethanol (TFE) concentration. Each peptide possesses only modest helical propensity in solution. Our data, which is different from what was observed in T4 lysozyme, show that the conformation of the duplicated sequence is determined by a balance of sequential and longer-range effects. Thus duplicating sequence need not mean duplicating structure. Proteins 2000;40:465-472.
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Thomas C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218-2685, USA.
Gittis
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Lattman
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D000465:Algorithms; D002942:Circular Dichroism; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D020440:Gene Duplication; D008836:Micrococcal Nuclease / Q000737:chemistry* / Q000235:genetics*; D008958:Models, Molecular; D009154:Mutation; D009842:Oligopeptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D020449:Repetitive Sequences, Amino Acid
D009842:Oligopeptides; D008836:Micrococcal Nuclease