Exploring the diversity of SPRY/B30.2-mediated interactions

The SPIa/Ryanodine receptor (SPRY)/B30.2 domain is one of the most common folds in higher eukaryotes. The human genome encodes 103 SPRY/B30.2 domains, several of which are involved in the immune response. Approximately 45% of human SPRY/B30.2-containing proteins are E3 ligases. The role and function of the majority of SPRY/B30.2 domains are still poorly understood, however, in several cases mutations in this domain have been linked to congenital disorders. The recent characterization of SPRY/B30.2-mediated protein interactions has provided evidence for a role of this domain as an adaptor module to assemble macromolecular complexes, analogous to Src homology (SH)2, SH3, and WW domains. However, functional and structural evidence suggests that SPRY/B30.2 is a more versatile fold, allowing a wide range of binding modes.