Yigong SHI

Research Area:
The main research focus in my Princeton laboratory (1998-2008) was to elucidate the underlying molecular mechanisms that govern the initiation, execution, and regulation of apoptosis. Towards this goal, we took an integrated approach combining X-ray crystallography, biochemistry, biophysics, and cell biology. We determined more than 40 crystal structures of important proteins and protein complexes that together regulate the onset and execution of apoptosis. These structures, together with associated biochemistry and cell biology, reveal the molecular mechanisms of initiator caspase recruitment by Apaf-1, initiator caspase activation, activation and inhibition of effector caspase, regulation of Apaf-1, and regulation of apoptosis in Drosophila and C. elegans. My laboratory at Tsinghua University became fully operational in April 2007. Here I expanded my research interests to include a set of new projects in membrane protein structure and function as well as macromolecular machineries. In collaboration with Nieng Yan’s group, we elucidated the structure of a novel ion channel FocA, which was thought to be an ion transporter. We reported the structures of an amino acid antiporter AdiC in both substrate-free and substrate-bound states, which reveal tantalizing clues about how the amino acid arginine is transported across cell membrane. These structures allow proposition of a detailed transport mechanism for the LeuT-type superfamily of membrane transporters. We also elucidated the crystal structure of an apoptosome – that from C. elegans. This structure reveals insights into how initiator caspases are activated.
 

Selected Publications:
1. Wang F, Mei Z, Qi Y, Yan C, Hu Q, Wang J, Shi Y. Structure and mechanism of the hexameric MecA-ClpC molecular machine. NATURE 471: 331-335, 2011
2. Qi S, Pang Y, Hu Q, Liu Q, Li H, Zhou Y, He T, Liang Q, Liu Y, Yuan X, Luo G, Li H, Wang J, Yan N, Shi Y. Crystal structure of the Caenorhabditis elegans apoptosome reveals an octameric assembly of CED-4. CELL 141(3):446-457, 2010
3. Zhang P, Wang JW, Shi YG. Structure and mechanism of the S component of a bacterial ECF transporter. NATURE 468: 717-720, 2010
4. Gao X, Zhou LJ, Jiao XY, Lu FR, Yan CY, Zeng X, Wang JW, Shi YG. Mechanism of substrate recognition and transport by an amino acid antiporter. NATURE 463: 828-832, 2010
5. Shi Y. Structure and Mechanism of Protein Serine/Threonine Phosphatases. CELL 139: 468-484, 2009
6. Wang Y, Huang YJ, Wang JW, Cheng C, Huang WJ, Lu PL, Xu YN, Wang PY, Yan N, Shi YG. Structure of the formate transporter FocA reveals a pentameric aquaporin-like channel. NATURE 462: 467-472, 2009
7. Gao X, Lu FR, Zhou LJ, Dang SY, Sun LF, Li XC, Wang JW, Shi YG. Structure and Mechanism of an Amino Acid Antiporter. SCIENCE 324: 1565-1568, 2009
8. Xing YN, Li Z, Chen Y, Stock JB, Jeffrey PD, Shi YG. Structural Mechnism of Demethylation and Inactivation of Protein Phosphatase 2A. CELL 133: 154-163, 2008