2011年3月18日，我室生物大分子结构与功能研究部姚雪彪教授研究组与人合作在JOURNAL OF BIOLOGICAL CHEMISTRY上发表题为Structure-Functional Analyses of CRHSP-24 Plasticity and Dynamics in Oxidative Stress Response的论文。

Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 286 Issue: 11 Pages: 9623-9635 Published: MAR 18 2011

Hou H (Hou, Hai)3, Wang FS (Wang, Fengsong)1,2, Zhang WC (Zhang, Wenchi)3, Wang DM (Wang, Dongmei)1,2, Li XM (Li, Xuemei)3, Bartlam M (Bartlam, Mark)4, Yao XB (Yao, Xuebiao)1,2, Rao ZH (Rao, Zihe)3,4
Addresses:
1. Anhui Key Lab Cellular Dynam & Chem Biol, Hefei 230027, Peoples R China
2. Hefei Natl Lab Phys Sci Nanoscale, Hefei 230027, Peoples R China
3. Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China
4. Nankai Univ, Coll Life Sci, Tianjin Key Lab Prot Sci, Tianjin 300071, Peoples R China
E-mail Addresses: yaoxb@ustc.edu.cn, raozh@xtal.tsinghua.edu.cn

Reprint Address: Yao, XB (reprint author), Anhui Key Lab Cellular Dynam & Chem Biol, Hefei 230027, Peoples R China

Abstract:
The cold shock domain (CSD) is an evolutionarily conserved nucleic acid binding domain that exhibits binding activity to RNA, ssDNA, and dsDNA. Mammalian CRHSP-24 contains CSD, but its structure-functional relationship has remained elusive. Here we report the crystal structure of human CRHSP-24 and characterization of the molecular trafficking of CRHSP-24 between stress granules and processing bodies in response to oxidative stress. The structure of CRHSP-24 determined by single-wavelength anomalous dispersion exhibits an alpha-helix and a compact beta-barrel formed by five curved anti-parallel beta strands. Ligand binding activity of the CSD is orchestrated by residues Ser(41) to Leu(43). Interestingly, a phosphomimetic S41D mutant abolishes the ssDNA binding in vitro and causes CRHSP-24 liberated from stress granules in vivo without apparent alternation of its localization to the processing bodies. This new class of phosphorylation-regulated interaction between the CSD and nucleic acids is unique in stress granule plasticity. Importantly, the association of CRHSP-24 with stress granules is blocked by PP4/PP2A inhibitor calyculin A as PP2A catalyzes the dephosphorylation of Ser(41) of CRHSP-24. Therefore, we speculate that CRHSP-24 participates in oxidative stress response via a dynamic and temporal association between stress granules and processing bodies.