Protein fold analysis of the B30.2-like domain

The B30.2-like domain occurs in some members of a diverse and growing famil y of proteins containing zinc-binding B-box motifs, whose functions include regulation of cell growth and differentiation. The B30.2-like domain is al so found in proteins without the zinc-binding motifs, such as butyrophilin (a transmembrane glycoprotein) and stonustoxin (a secreted cytolytic toxin) , Currently, the function for the B30.2-like domain is not clear and the st ructure of a protein containing this domain has not been solved. The second ary structure prediction methods indicate that the B30.2-like domain consis ts of fifteen or fewer beta-strands. Fold recognition methods identified di fferent structural topologies for the B30.2-like domains. Secondary structu re prediction, deletion and lack of local sequence identity at the C-termin al region for certain members of the family, and packing of known core stru ctures suggest that a structure containing two beta domains is the most pro bable of these folds. The most C-terminal sequence motif predicted to be a beta-strand in all B30.2-like domains is a potential subdomain boundary bas ed on the sequence-structure alignments. Models of the B30.2-like domains w ere built based on immunoglobulin-like folds identified by the fold recogni tion methods to evaluate the possibility of the B30.2 domain adopting known folds and infer putative functional sites. The SPRY domain has been identi fied as a subdomain within the B30.2-like domain. If the B30.2-like domain is a subclass of the SPRY domain family, then this analysis would suggest t hat the SPRY domains are members of the immunoglobulin superfamily, (C) 199 9 Wiley-Liss, Inc.