SPSB1 + PAR4 peptide

SPSB1 + PAR4 peptide

SPSB1 + PAR4 peptide: Human SPRY domain-containing SOCS box protein SSB-1 in complex with PAR4 peptide
PDB Code: 2JK9
Description
Human SPRY-domain-containing SOCS box protein 1 (SPSB1 or SSB-1) belongs to a family of four proteins containing an N-terminal SPRY (or B30.2) domain and a C-terminal SOCS box (SPSB1-4). The SOCS box functions as an adaptor domain that binds ElonginBC and mediates further assembly with cullin ubiquitin ligases. The SPRY domain was first identified in the dual-specificity kinase splA and ryanodine receptors and is proposed to function as a protein-protein recognition domain. Several human diseases arise from mutations in genes coding for SPRY domain containing proteins, for example mutations in the MEFV gene are associated with familial Mediterranean fever.
SPSB1 is expressed in the ovary in granulosa cells at all stages of follicular development and is therefore proposed to regulate granulosa cell physiology. It is highly conserved with the Drosophila homologue Gustavus for which structures have defined interactions with ElonginBC and an Asp-Ile-Asn-Asn-Asn-Asn recognition motif from the RNA helicase VASA. The human SPSB1 SPRY domain has been shown to bind the MET receptor tyrosine kinase and to regulate the HGF-induced Erk-Elk-1-SRE pathway.  Here we determined the crystal structure of SPSB1 in complex with a high affinity peptide derived from prostate apoptosis response protein-4 (PARW or PAR-4) (KD = 180 nM). When overexpressed PAR-4 sensitizes cancer cells to diverse apoptotic stimuli causing tumour regression in animal models.

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