From fold to function predictions: an apoptosis regulator protein BID

With the rapidly increasing pace of genome sequencing projects and the resu lting flood of predicted amino acid sequences of uncharacterized proteins, protein sequence analysis, and in particular, protein structure prediction is quickly gaining in importance. Prediction algorithms can be used for pre liminary annotation of newly sequenced proteins and, at least in some cases , provide insights into their function and specific mode of action. Such an notations for several microbial genomes were performed by several groups an d placed in public domain for evaluation. An example presented in this work comes from a related project of structural and functional predictions for proteins involved in the process of controlled cell death (apoptosis). The BID protein belongs to an important class of regulators of apoptosis identi fied by short sequence motifs. Here, several fold prediction methods are us ed to build a series of three-dimensional models. Structure analysis of the models with reference to the biological data available allows selection of the most appropriate model. It is found that the most likely structural mo del of BID is built on the structure of Bcl-X-L. The model is discussed in terms of experimental data on specific proteolytic cleavage of BID and its effect on BID interactions with other proteins and membranes. (C) 2000 Else vier Science Ltd. All rights reserved.