Yigong Shi


Affiliation: Tsinghua University
Country: China


  1. Zhang X, Wang Q, Wu J, Wang J, Shi Y, Liu M. Crystal structure of human lysyl oxidase-like 2 (hLOXL2) in a precursor state. Proc Natl Acad Sci U S A. 2018;115:3828-3833 pubmed publisher
    ..The structure presented here establishes an important foundation for understanding the structure-function relationship of LOX proteins and will facilitate LOX-targeting drug discovery. ..
  2. Pang Y, Bai X, Yan C, Hao Q, Chen Z, Wang J, et al. Structure of the apoptosome: mechanistic insights into activation of an initiator caspase from Drosophila. Genes Dev. 2015;29:277-87 pubmed publisher
    ..These findings reveal important mechanistic insights into the activation of initiator caspase by the apoptosome. ..
  3. Luan B, Huang X, Wu J, Mei Z, Wang Y, Xue X, et al. Structure of an endogenous yeast 26S proteasome reveals two major conformational states. Proc Natl Acad Sci U S A. 2016;113:2642-7 pubmed publisher
    ..Structure-guided biochemical analysis reveals enhanced deubiquitylating enzyme activity of Rpn11 upon assembly of the lid. Our structures serve as a molecular basis for mechanistic understanding of proteasome function. ..
  4. Wan R, Bai R, Yan C, Lei J, Shi Y. Structures of the Catalytically Activated Yeast Spliceosome Reveal the Mechanism of Branching. Cell. 2019;: pubmed publisher
    ..This analysis reveals the functional mechanism of Yju2 and Cwc25 in branching. These structures on different pre-mRNAs reveal substrate-specific conformations of the spliceosome in a major functional state. ..
  5. Zhang X, Zhan X, Yan C, Zhang W, Liu D, Lei J, et al. Structures of the human spliceosomes before and after release of the ligated exon. Cell Res. 2019;29:274-285 pubmed publisher
    ..Comparison of these three late-stage human spliceosomes reveals mechanistic insights into exon release and spliceosome disassembly. ..
  6. Zhou R, Yang G, Guo X, Zhou Q, Lei J, Shi Y. Recognition of the amyloid precursor protein by human γ-secretase. Science. 2019;363: pubmed publisher
    ..This structure, together with that of γ-secretase bound to Notch, reveal contrasting features of substrate binding, which may be applied toward the design of substrate-specific inhibitors. ..
  7. Yang G, Zhou R, Zhou Q, Guo X, Yan C, Ke M, et al. Structural basis of Notch recognition by human γ-secretase. Nature. 2019;565:192-197 pubmed publisher
    ..PS1 undergoes pronounced conformational rearrangement upon substrate binding. These features reveal the structural basis of Notch recognition and have implications for the recruitment of the amyloid precursor protein by γ-secretase. ..
  8. Zhan X, Yan C, Zhang X, Lei J, Shi Y. Structures of the human pre-catalytic spliceosome and its precursor spliceosome. Cell Res. 2018;28:1129-1140 pubmed publisher
    ..Structural analysis reveals mechanistic insights into the assembly and activation of the human spliceosome. ..
  9. Su Q, Hu F, Ge X, Lei J, Yu S, Wang T, et al. Structure of the human PKD1-PKD2 complex. Science. 2018;361: pubmed publisher
    ..The PKD1-PKD2 complex structure establishes a framework for dissecting the function and disease mechanisms of the PKD proteins. ..

More Information


  1. Bai R, Wan R, Yan C, Lei J, Shi Y. Structures of the fully assembled Saccharomyces cerevisiae spliceosome before activation. Science. 2018;360:1423-1429 pubmed publisher
    ..Structural analysis reveals the mechanism of assembly and activation for the yeast spliceosome. ..
  2. Hu Q, Wu D, Chen W, Yan Z, Yan C, He T, et al. Molecular determinants of caspase-9 activation by the Apaf-1 apoptosome. Proc Natl Acad Sci U S A. 2014;111:16254-61 pubmed publisher
    ..Together, these findings reveal mechanistic insights into the activation of caspase-9 by the Apaf-1 apoptosome and support the induced conformation model for initiator caspase activation by adaptor complexes. ..
  3. Dang S, Wu S, Wang J, Li H, Huang M, He W, et al. Cleavage of amyloid precursor protein by an archaeal presenilin homologue PSH. Proc Natl Acad Sci U S A. 2015;112:3344-9 pubmed publisher
    ..These findings identify PSH as a surrogate protease for the screening of agents that may regulate the protease activity and the cleavage preference of γ-secretase. ..
  4. Shi Y. A glimpse of structural biology through X-ray crystallography. Cell. 2014;159:995-1014 pubmed publisher
  5. Hang J, Wan R, Yan C, Shi Y. Structural basis of pre-mRNA splicing. Science. 2015;349:1191-8 pubmed publisher
    ..Thus, the spliceosome is in essence a protein-directed ribozyme, with the protein components essential for the delivery of critical RNA molecules into close proximity of one another at the right time for the splicing reaction. ..
  6. Yan C, Wan R, Bai R, Huang G, Shi Y. Structure of a yeast activated spliceosome at 3.5 Å resolution. Science. 2016;353:904-11 pubmed publisher
    ..This structure, together with those determined earlier, outlines a molecular framework for the pre-mRNA splicing reaction. ..
  7. Wan R, Yan C, Bai R, Huang G, Shi Y. Structure of a yeast catalytic step I spliceosome at 3.4 Å resolution. Science. 2016;353:895-904 pubmed publisher
    ..These features, representing the conformation of the spliceosome after the first-step reaction, predict structural changes that are needed for the execution of the second-step transesterification reaction. ..
  8. Sun L, Zhou R, Yang G, Shi Y. Analysis of 138 pathogenic mutations in presenilin-1 on the in vitro production of Aβ42 and Aβ40 peptides by γ-secretase. Proc Natl Acad Sci U S A. 2017;114:E476-E485 pubmed publisher
    ..There is no statistically significant correlation between the Aβ42/Aβ40 ratio produced by a γ-secretase variant containing a specific PS1 mutation and the mean age at onset of patients from whom the mutation was isolated. ..
  9. Jiang T, Liu M, Wu J, Shi Y. Structural and biochemical analysis of Bcl-2 interaction with the hepatitis B virus protein HBx. Proc Natl Acad Sci U S A. 2016;113:2074-9 pubmed publisher
    ..These observations suggest that HBx may modulate Bcl-2 function in a way that is different from that of the classical BH3-only proteins. ..
  10. Sun L, Li X, Shi Y. Structural biology of intramembrane proteases: mechanistic insights from rhomboid and S2P to γ-secretase. Curr Opin Struct Biol. 2016;37:97-107 pubmed publisher
    ..In this review, we discuss the shared as well as unique features of these intramembrane proteases, with a focus on presenilin-the catalytic component of γ-secretase. ..
  11. Yan C, Wan R, Bai R, Huang G, Shi Y. Structure of a yeast step II catalytically activated spliceosome. Science. 2017;355:149-155 pubmed publisher
    ..These structural features, together with those reported for other spliceosomal complexes, yield a near-complete mechanistic picture on the splicing cycle. ..
  12. Li Y, Zhou M, Hu Q, Bai X, Huang W, Scheres S, et al. Mechanistic insights into caspase-9 activation by the structure of the apoptosome holoenzyme. Proc Natl Acad Sci U S A. 2017;114:1542-1547 pubmed publisher
    ..These structural and biochemical findings demonstrate that the apoptosome activates caspase-9 at least in part through sequestration of the inhibitory CARD domain. ..
  13. Bai R, Yan C, Wan R, Lei J, Shi Y. Structure of the Post-catalytic Spliceosome from Saccharomyces cerevisiae. Cell. 2017;171:1589-1598.e8 pubmed publisher
    ..The 3'SS is stabilized through an interaction with the 1585-loop of Prp8. The P complex structure provides a view on splice junction formation critical for understanding the complete splicing cycle. ..
  14. Wan R, Yan C, Bai R, Lei J, Shi Y. Structure of an Intron Lariat Spliceosome from Saccharomyces cerevisiae. Cell. 2017;171:120-132.e12 pubmed publisher
    ..These structural features suggest a plausible mechanism for the disassembly of the ILS complex. ..
  15. Shi Y. The Spliceosome: A Protein-Directed Metalloribozyme. J Mol Biol. 2017;429:2640-2653 pubmed publisher
    ..The spliceosome is proven to be a protein-directed metalloribozyme. ..
  16. Yang G, Zhou R, Shi Y. Cryo-EM structures of human ?-secretase. Curr Opin Struct Biol. 2017;46:55-64 pubmed publisher
    ..Here we summarize the methods involved and discuss structural features of ?-secretase and the associated functional insights. ..
  17. Zhang X, Yan C, Hang J, Finci L, Lei J, Shi Y. An Atomic Structure of the Human Spliceosome. Cell. 2017;169:918-929.e14 pubmed publisher
    ..These structural features reveal important mechanistic insights into exon ligation. ..
  18. Shi Y. Serine/threonine phosphatases: mechanism through structure. Cell. 2009;139:468-84 pubmed publisher
    ..Here, we discuss biochemical and structural investigations that advance the mechanistic understanding of the three major classes of PSPs, with a focus on PP2A. ..
  19. Sun L, Zhao L, Yang G, Yan C, Zhou R, Zhou X, et al. Structural basis of human γ-secretase assembly. Proc Natl Acad Sci U S A. 2015;112:6003-8 pubmed publisher
    ..TM6 and TM7 in PS1, which harbor the catalytic aspartate residues, are located on the convex side of the TM horseshoe. This structure serves as an important framework for understanding the function and mechanism of γ-secretase. ..
  20. Xie T, Yan C, Zhou R, Zhao Y, Sun L, Yang G, et al. Crystal structure of the γ-secretase component nicastrin. Proc Natl Acad Sci U S A. 2014;111:13349-54 pubmed publisher
    ..These structural features suggest a working model of nicastrin function. Analysis of nicastrin structure provides insights into the assembly and architecture of the γ-secretase complex. ..