A novel dimerization module in Gemin5 is critical for protein recruitment and translation control

Abstract

The versatile multifunctional protein Gemin5 is involved in small nuclear ribonucleoproteins (snRNPs) assembly, ribosome binding, and translation control through distinct domains located at the protein ends. However, the structure and function of the central moiety of Gemin5 remained unknown. Here, we solved the crystal structure of an extended tetratricopeptide (TPR)-like domain in the middle region of Gemin5, demonstrating that it self-assembles into a canoe-shaped dimer. Mass spectrometry analysis shows that this dimerization module is functional in living cells and drives the interaction between p85, a viral-induced Gemin5 cleavage fragment, and the full-length Gemin5. In contrast, disruption of the dimerization surface by a point mutation in the TPR-like domain prevents this interaction and abrogates the translation enhancement induced by p85. The structural characterization of this unprecedented dimerization domain provides the mechanistic basis for a role of the middle region of Gemin5 as a key mediator of protein-protein interactions.\n\nHIGHLIGHTS- The crystal structure of a central region of Gemin5 reveals a novel dimerization domain\n- The proteolytic product of Gemin5 (p85) recruits the endogenous protein through the dimerization module\n- The dimerization capability of Gemin5 determines the factors recruited in human cells\n- Disruption of the dimerization domain impairs p85 ability to stimulate translation\n\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC=\"FIGDIR/small/654111v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (78K):\norg.highwire.dtl.DTLVardef@9d8e69org.highwire.dtl.DTLVardef@1f0a453org.highwire.dtl.DTLVardef@1b486c4org.highwire.dtl.DTLVardef@fbb5ea_HPS_FORMAT_FIGEXP M_FIG Graphical abstract\n\nC_FIG