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