The β-propeller is an all-β highly symmetric fold. Based on the crystal structure of Gβ, which contains seven WD-repeats with a one-to-one correspondence to the structural repeats of its seven-bladed propeller, we predict that the entire family of WD-repeat-containing proteins fold into β-propellers, thus constituting a subfamily of the propeller structural family.; WD-repeat proteins contain multiple copies of a sequence repeat approximately forty amino adds long, that most often ends with Trp-Asp (WD). The functional diversity among members of this family is unusual given their high sequence similarity, which leads to the conclusion that the role of the WD-repeat is structural rather than functional. The goal of the work presented here was to develop a procedure for construction of structural models for all WD-repeat proteins.; In order to improve the accuracy of our modeling efforts, we carried out extensive characterization of the β-propeller fold. Using energetic criteria, we determined the positions which are important for the stability of the propeller. Three inter-β-blade contacts were identified that are shared by amino acids in equivalent positions in the majority of the known propellers. This structural information was incorporated into a regular expression that represents conserved elements of the WD-repeat. Over 1000 WD-repeats were identified when all existing sequence databases were searched with this expression. Using three criteria, similarity in WD-repeat number, similarity in the predicted outer surface, and similarity in non-WD-domains, WD-repeat-containing proteins were classified into functional subfamilies (regular expression, alignments and subfamily classifications available at http:// bmerc-www.bu.edu/wdrepeat/).; We also described various geometric features of the β-propeller fold and examined their variation as a function of the number of β-blades. We combined this information with the WD-repeat conserved features and constructed ‘generic’ backbone structural models for proteins with four to ten WD-repeats. In a cross-validated experiment, the backbone coordinates of Gβ were predicted to 0.97Å core RMSD. Such structural models enhance our understanding of the structure/function relationships of WD-repeat proteins, and serve as guides for improved experimental design of pharmaceutical reagents, prediction of binding surfaces and active sites and targets for site-directed mutational analysis.
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