Identifying natural substrates for chaperonins using a sequence-based approach.
The Escherichia coli chaperonin machinery, GroEL, assists the folding of a number of proteins. We describe a sequence-based approach to identify the natural substrate proteins (SPs) for GroEL. Our method is based on the hypothesis that natural SPs are those that contain patterns of residues similar to those found in either GroES mobile loop and/or strongly binding peptide in complex with GroEL. The method is validated by comparing the predicted results with experimentally determined natural SPs for GroEL. We have searched for such patterns in five genomes. In the E. coli genome, we identify 1422 (about one-third) sequences that are putative natural SPs. In Saccharomyces cerevisiae, 2885 (32%) of sequences can be natural substrates for Hsp60, which is the analog of GroEL. The precise number of natural SPs is shown to be a function of the number of contacts an SP makes with the apical domain (N(C)) and the number of binding sites (N(B)) in the oligomer with which it interacts. For known SPs for GroEL, we find approximately 4 < N(C) < 5 and 2 <or= N(B) <or= 4. A limited analysis of the predicted binding sequences shows that they do not adopt any preferred secondary structure. Our method also predicts the putative binding regions in the identified SPs. The results of our study show that a variety of SPs, associated with diverse functions, can interact with GroEL.
Stan
George
G
Laboratory of Computational Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Brooks
Bernard R
BR
Lorimer
George H
GH
Thirumalai
D
D
D001665:Binding Sites; D018834:Chaperonin 60 / Q000737:chemistry*; D018833:Chaperonins / Q000737:chemistry*; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D004926:Escherichia coli / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics; D012680:Sensitivity and Specificity; D020539:Sequence Analysis, Protein; D013379:Substrate Specificity
D018834:Chaperonin 60; D018833:Chaperonins