The SPRY domain-containing SOCS Box (SPSB; SSB) proteins
The SPSB protein family (SPSB-1 to -4) is distinguished by the presence of a central SPRY protein-interaction domain and a C-terminal SOCS box motif. The SOCS box motif recruits an E3 ubiquitin ligase complex, which polyubiquitinates proteins targeted by interaction with the SPRY domain, resulting in their proteasomal degradation.
The number of known SPRY domains now exceeds 1600, with 74 proteins encoded for in the human genome. SPRY-containing proteins have diverse biological roles including in development and the innate immune response.
We are interested in potential binding partners for the SPSB proteins and, from a more global perspective, how the SPRY domain per se interacts with its target proteins.
The SPSB SPRY domains interact with a linear peptide sequence in the N-terminus of iNOS. We have obtained detailed structural information on the binding interface and are now interested in identifying lead compounds to disrupt this interaction by screening fragment libraries and rational peptide design.
