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Minghui Li
Publisher:高雪  Time2017-09-28 View:30

  

Minghui Li


Phone: 1-(646)912-2854
Email:   limh9812@yahoo.comminghuili@hit.edu.cn
Research   Area: Structural biology of membrane proteins

 


Minghui Li graduated with a Bachelor's degree in Biochemistry from the Department of Molecular Biology, Jilin University, in 1997. He was trained as a protein crystallographer at the Institute of Biophysics, Chinese Academy of Sciences, and got Ph.D. in 2003. He worked on the structural studies of pyridoxal kinase, a key enzyme functioning in the metabolism of vitamin B6.  The three dimensional structures of the enzyme and complexes formed by the enzyme and its substrates and products advanced the understanding of the specificity and catalytic mechanism of this enzyme. At Columbia University, Dr. Li’s research has been focused on the structure-function relationship of ion channels. Ion channels are membrane proteins forming narrow tunnels and allow certain ions to pass through the membrane. They play critical roles in numerous biological processes, such as nerve impulse, muscle contraction, neurotransmitter release, hormones secretion, gene transcription regulation, etc. Ion channels are activated and regulated by different factors. Their dysfunction causes disorders in humans. One of Dr. Li’s research interests was to solve the structures of soluble fragments or domains of ion channels, such as the beta-subunit of voltage-gated calcium channels, the coiled coil domain of TRPP channels, and the I-II linker of the TRPML1 channel. Those structures shed light on the assembly and regulations of those channels. Another more challenging direction Dr. Li has taken is to solve the structures of full-length ion channels. By overcoming the intrinsic difficulty in the expression and purification of membrane proteins and utilizing the rapid growing high resolution cryo-electron microscopy, Dr. Li and collaborators have successfully determined the structures of two ion channels, cyclic nucleotide gated (CNG) channel and TRPML3 channel. These full length ion channel structures and structure-based functional studies provide significant insights into the ion permeation, ligand activation and regulation of these channels. Dr. Li’s lab at Harbin Institute of Technology will work on structural biology of important membrane proteins including ion channels, and structure based functional studies of those proteins.

  

Research Interests

Structural biology of membrane proteins

Structural mechanisms of ion channel gating and regulation.

Structure determination of full length ion channels by cryo-electron microscopy.

Three dimensional structure determination of important regulatory soluble fragments of ion channels by X-ray crystallography.

Structure based functional studies on ion channels.

  

Techniques and Tools in the Lab

Molecular cloning

Cell culture

Overexpression of proteins using bacteria, insect, and mammalian cells

Isolation and purification of soluble and membrane proteins

Protein crystallization

X-ray crystallography

Single particle cryo-electron microscopy

Protein structure model building, refinement and analysis

Patch clamp recording of ion channels

  

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. Cryo-EM Structures of the Human Endolysosomal TRPML3 Channel in Distinct States.Submitted. (* 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