3)　　 Structure and function of membrane proteins and protein complexes 

♦　  Atomic model of a cypovirus built from cryo-EM structure

Taking advantage of the state-of-the-art 300KV Titan Krios FEG transmission cryo electron microscope recently installed in the bio-imaging laboratory of IBP, the researchers reconstructed the 3D density map of a cypovirus (CPV) from Reoviridae at near-atomic resolution (3.9 Å) using cryoEM single particle analysis, and built the first full atomic model of this virus. The article presents the first reported atomic model of a macromolecule built from a cryo-EM structure in China. It also represents the first full atomic model (with amino acid side chains) built exclusively from CCD image data in the high resolution cryoEM area (PNAS, 2011).

♦　  Aberrant nuclear architecture in neural stem cells of Parkinson’s disease

To reveal the pathogenic process during aging in PD, Professor LIU Guanghui and his colleague employed the human pluripotent stem cell technologies and the clinical patients’ samples, and demonstrated the nuclear defects in the neural cells of PD patients. They reprogrammed the skin cells from PD patients and generated the pluripotent stem cells (iPSCs) carrying a known genetic mutation (LRRK2/G2019S) associated with both familial and sporadic PD cases, and directed the PD iPSC cells differentiated to neural stem cells (NSCs). They have found that the gene mutation results in the aberrant nucleus architecture, forming the pedal-like nuclei in neural stem cells (NSCs) during in vitro aging. The deformed NSC nuclear shape is accompanied with decreased abilities of clonal expansion, neural differentiation, and resistance to stresses, which partially explain PD syndrome. Damages to the cells caused by the LRRK2 mutation can be rescued with the targeted gene editing technologies to correct the LRRK mutation or chemical inhibitor of LRRK2, which provides a new hope to develop drugs for PD patients carrying this mutation. Finally, Professor Liu validated and confirmed nuclear envelope impairments in the brain samples from Parkinson's disease patients (Nature, 2012).

♦　  Structural Analysis of the STING Adaptor Protein Reveals a Hydrophobic Dimer Interface and Mode of Cyclic di-GMP Binding

A stimulator of interferon genes (STING), is an essential signaling molecule for DNA and cyclic di-GMP (c-di-GMP)-mediated type I interferon (IFN) production via TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) pathway.The structural, functional, and mutagenesis data unravel several hitherto unknown aspects of STING and shed light on its mechanism of activation (Immunity, 2012).

 

 ♦　  Structural study of two different enterovirus 71 capsids

Professor Rao Zihe and his group resolved the crystal structure of mature full particle of EV71, as well as that of a kind of pre-mature empty particle of it. Compared with the mature full particle, the empty particle has notable openings on the two-fold and the typical canyon of its capsid, with the diameter of the particle expand about 4%. The new structural knowledge provided by this study might facilitate the development of generic therapies against enteroviruses, some of which, for instance EV71, represent serious threats to human and/or animal health (Nat Struc Mol Biol, 2012).