Alleviation of a defect in protein folding by increasing the rate of subunit assembly.
Understanding the nature of protein grammar is critical because amino acid substitutions in some proteins cause misfolding and aggregation of the mutant protein resulting in a disease state. Amino acid substitutions in phage P22 coat protein, known as tsf (temperature-sensitive folding) mutations, cause folding defects that result in aggregation at high temperatures. We have isolated global su (suppressor) amino acid substitutions that alleviate the tsf phenotype in coat protein (Aramli, L. A., and Teschke, C. M. (1999) J. Biol. Chem. 274, 22217-22224). Unexpectedly, we found that a global su amino acid substitution in tsf coat proteins made aggregation worse and that the tsf phenotype was suppressed by increasing the rate of subunit assembly, thereby decreasing the concentration of aggregation-prone folding intermediates.
Aramli
L A
LA
University of Connecticut, Department of Molecular and Cell Biology, 75 N. Eagleville Road, Storrs, CT 06269-3125, USA.
Teschke
C M
CM
D019943:Amino Acid Substitution; D017100:Bacteriophage P22 / Q000737:chemistry / Q000235:genetics; D002213:Capsid / Q000737:chemistry* / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D009154:Mutation; D010641:Phenotype; D011487:Protein Conformation; D017510:Protein Folding; D013696:Temperature; D014105:Tosyl Compounds; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics; D015678:Viral Structural Proteins / Q000737:chemistry / Q000235:genetics
D014105:Tosyl Compounds; D014764:Viral Proteins; D015678:Viral Structural Proteins; C111088:scaffolding protein, bacteriophage P22; C068650:arf protein, Enterobacteria phage P22; C003614:4-toluenesulfonyl fluoride