Identifying determinants of folding and activity for a protein of unknown structure.
We have generated an extensive genetic map of functionally allowed and/or structurally allowed amino acid substitutions in Arc repressor, a DNA binding protein of unknown structure. Analysis of the allowed substitution patterns identifies residues that are likely to be involved in protein function and identifies side chains that play important structural roles, including residues likely to form the hydrophobic core. The identities of approximately one-third of the residues in Arc repressor are functionally important, about one-half are structurally important, and the remainder are unimportant for either structure or function. The patterns of obligatory hydrophobic positions permit strong predictions of secondary structure.
Bowie
J U
JU
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139.
Sauer
R T
RT
D000595:Amino Acid Sequence; D001483:Base Sequence; D002942:Circular Dichroism; D003062:Codon / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004355:Drug Stability; D005796:Genes; D005798:Genes, Bacterial; D005813:Genes, Synthetic; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D011489:Protein Denaturation; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins
D003062:Codon; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins