Minghui Li graduated with a Bachelor's degree in Biochemistry from  Jilin University, in 1997. He received his PhD in 2003 from the Institute of  Biophysics, Chinese Academy of Sciences. During his PhD, he worked on the  structural studies of pyridoxal kinase, a key enzyme functioning in the  metabolism of vitamin B6.

Dr. Li then worked at Columbia University on the structure-function  relationship of ion channels. He solved the structure of important soluble  fragments or domains of ion channels, which help greatly to understand the  assembly and regulations of those channels. Dr. Li has also been devoted to the  structure determination of full-length ion channels. Dr. Li and collaborators  have successfully solved the structures of two ion channels, cyclic nucleotide  gated (CNG) channel in a liganded open state, and TRPML3 channel in the closed,  agonist-activated, and low-pH-inhibited states. These structures and  structure-based functional studies provide significant insights into the ion  permeation, ligand activation and regulation of these channels.

Dr. Li joined the HIT Center for Life Sciences (HCLS) in December  2017. His lab work on structural studies and structure-based functional  studies of important membrane proteins.

Research Interests

Structural biology of membrane proteins: membrane proteins are  located on the plasma membrane and organellar membrane. They participate various  energy transduction and intramembrane catalytic process, and control the  transmembrane transportation of substance and transmembrane signal transduction.  Membrane proteins play critical roles in so many biological process that their  dysfunction causes many disorders in humans. Membrane proteins are the targets  of most drugs on the market. Three-dimensional structures of membrane proteins  are essential for understanding the mechanisms of their function and regulation.  They also provide invaluable information for membrane protein targeted drug  design.

We work on the structure studies of important membrane proteins  including ion channels, transporters, and membrane receptors using cryo-electron  microscopy and X-ray crystallography. Determination of the three-dimensional  structure of full length membrane proteins or their important structural  domains, together with structure-guided functional studies, will help greatly on  the elucidation of the mechanism of these proteins.

Techniques and Tools in the Lab

Molecular cloning and Cell culture

Overexpression of proteins in bacteria, insect, and  mammalian cells

Isolation and purification of soluble and  membrane proteins

Protein X-ray crystallography

Single particle cryo-electron microscopy

Protein structure model building, refinement and analysis

Selected Publications

1. Li M*,  Zhou X*, Wang S*, Michailidis I, Gong Y, Su D, Li H, Li X, Yang J. (2017)  Structure of a eukaryotic cyclic-nucleotide-gated  channel.Nature.  542:60-65 (* Equal contribution)

2. Li M*,  Zhang WK*, Benvin NM*, Zhou X, Su D, Li H, Wang S, Michailidis IE, Tong L, Li X,  Yang J. (2017) Structural basis of dual Ca2+/pH regulation of the endolysosomal  TRPML1 channel.Nat  Struct Mol Biol.24:205-213  (* Equal contribution)

3. Zhou X*,Li M*, Su D*, Jia Q, Li H, Li X, Yang J. (2017)Cryo-EM structures of the human endolysosomal TRPML3 channel in three  distinct states. Nat Struct Mol Biol..24 : 1146-1154 (* Equal contribution)

4. Yu  Y, Ulbrich MH,Li  M,  Dobbins S, Zhang,  WK, Tong L, Isacoff EY, Yang, J. (2012) Molecular mechanism of the assembly of  an acid-sensing receptor ion channel complex.Nat  Commun.3:1252

5. Li M, Yu Y, YangJ.(2011)  Structural biology of TRP channels.Adv  Exp Med Biol.704:1-23(review)

6. Zhu  J, Yu Y, Ulbrich MH,Li  M,  Isacoff EY, Honig B, YangJ. (2011) Structural model of the TRPP2/PKD1 C-terminal  coiled-coil complex produced by a combined computational and experimental  approach.Proc  Natl Acad Sci U S A.108:10133-10138

7. Yu  Y, Ulbrich MH,Li  M,  Buraei Z, Chen XZ, Ong AC, Tong L, Isacoff EY, Yang, J. (2009) Structural and  molecular basis of the assembly of the TRPP2/PKD1  complex.Proc  Natl Acad Sci U S A.106:11558-11563

8. Tang  L,Li  M,  Cao P, Wang F, Chang WR, Bach S, Reinhardt J, Ferandin Y, Galons H, Wan Y, Gray  N, Meijer L, Jiang T, Liang DC.. (2005) Crystal structure of pyridoxal kinase in  complex with roscovitine and derivatives. J  Biol Chem.280:31220-31229

9. Chen  YH,Li  M,  Zhang Y, He LL, Yamada Y, Fitzmaurice A, Shen Y, Zhang H, Tong L, YangJ. (2004)  Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca2+  channels.Nature.429:675-680

10. Li M,  Kwok F, Chang WR, Liu SQ, Lo SC, Zhang JP, Jiang T, Liang DC(2004)  Conformational changes in the reaction of pyridoxal  kinase.J  Biol Chem.279:17459-17465

11. Li M,  Kwok F, Chang WR, Lau CK, Zhang JP, LoSC, Jiang T, Liang DC. (2002). Crystal  structure of brain pyridoxal kinase, a novel member of the ribokinase  superfamily.J  Biol Chem.277:46385-46390

12. Li M,  Kwok F, An XM, Chang WR, Lau CK, Zhang JP, Liu SQ, Leung YC, Jiang T, Liang DC.  (2002). Crystallization and preliminary crystallographic studies of pyridoxal  kinase from sheep brain.Acta  Crystallogr D Biol Crystallogr.  58:1479-1481