The human protein Caprin1 is a prototypic member of a novel protein family that plays many essential functions, including promoting cellular proliferation, mediating innate antiviral response, regulating neuron development, and participating in stress response. Caprin1 has been implicated in the pathogenesis of many human diseases such as cancer, viral infection, hearing loss, and neurodegenerative disorders. The various functions of Caprin1 are dictated by its interaction with various partners. It is therefore crucial to reveal the molecular structures of Caprin1 protein complexes. We have recently determined the crystal structure of the dimerization domain of human Caprin1, representing the first structural study of this important protein. Building on this success, a combined structural and biochemical study is proposed to further investigate the molecular basis for Caprin1 functions, with an emphasis on its interaction with partner proteins including G3BP1, FMRP, and the Japanese encephalitis virus core protein. Results from the study will provide the much needed structural knowledge regarding the function, regulation, and specificity of Caprin1.
Caprin1 is a biologically and pathophysiologically important human protein that assumes many important functions, depending on the formation of various multi-protein complexes. The overall goal of this proposal is to elucidate some of the key molecular structures underlying the functions of Caprin1. Results from the study will provide critical insights into the molecular mechanisms governing the functions of Caprin1.
| Wu, Yuhong; Zhu, Jiang; Huang, Xiaolan et al. (2018) Crystal structure of a dimerization domain of human Caprin-2: similar overall dimeric fold but different molecular surface properties to that of human Caprin-1. J Biomol Struct Dyn :1-23 |
| Wu, Yuhong; Zhu, Jiang; Huang, Xiaolan et al. (2016) 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. Acta Crystallogr D Struct Biol 72:718-27 |
| Wu, Yuhong; Zhu, Jiang; Huang, Xiaolan et al. (2015) Bacterial expression and preliminary crystallographic studies of a 149-residue fragment of human Caprin-1. Acta Crystallogr F Struct Biol Commun 71:324-9 |
