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Crystal structure of a dimerization domain of human Caprin‐1: insights into the assembly of an evolutionarily conserved ribonucleoprotein complex consisting of Caprin‐1, FMRP and G3BP1
Author(s) -
Wu Yuhong,
Zhu Jiang,
Huang Xiaolan,
Du Zhihua
Publication year - 2016
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.374
H-Index - 138
ISSN - 2059-7983
DOI - 10.1107/s2059798316004903
Subject(s) - biology , protein structure , microbiology and biotechnology , ribonucleoprotein , peptide sequence , caenorhabditis elegans , crystallography , chemistry , genetics , biochemistry , rna , gene
Caprin‐1 plays roles in many important biological processes, including cellular proliferation, innate immune response, stress response and synaptic plasticity. Caprin‐1 has been implicated in several human diseases, including osteosarcoma, breast cancer, viral infection, hearing loss and neurodegenerative disorders. The functions of Caprin‐1 depend on its molecular‐interaction network. Direct interactions have been established between Caprin‐1 and the fragile X mental retardation protein (FMRP), Ras GAP‐activating protein‐binding protein 1 (G3BP1) and the Japanese encephalitis virus (JEV) core protein. Here, crystal structures of a fragment (residues 132–251) of Caprin‐1, which adopts a novel all‐α‐helical fold and mediates homodimerization through a substantial interface, are reported. Homodimerization creates a large and highly negatively charged concave surface suggestive of a protein‐binding groove. The FMRP‐interacting sequence motif forms an integral α‐helix in the dimeric Caprin‐1 structure in such a way that the binding of FMRP would not disrupt the homodimerization of Caprin‐1. Based on insights from the structures and existing biochemical data, the existence of an evolutionarily conserved ribonucleoprotein (RNP) complex consisting of Caprin‐1, FMRP and G3BP1 is proposed. The JEV core protein may bind Caprin‐1 at the negatively charged putative protein‐binding groove and an adjacent E‐rich sequence to hijack the RNP complex.