Lie Wang

1. Determined high-resolution cryo-EM structures of human SFN14, identifying a putative RNA-recognition site and capturing two distinct conformational states associated with RNA binding, providing mechanistic insight into RNA-mediated regulation. 2. Solved a 1.9 Å cryo-EM structure of AqpZ using an ALFA tag/nanobody strategy, achieving near-atomic resolution. Discovered an unexpected oligomeric assembly and resolved bound lipid molecules, suggesting structural determinants of membrane protein stability and function. 3. Elucidated the structure and catalytic mechanism of phosphatidylserine synthase 2 (PTDSS2) through high-resolution cryo-EM. Defined substrate and cation binding sites and uncovered a previously unreported Ca²⁺-dependent phospholipase D (PLD) activity using fluorescent substrate assays, expanding functional understanding of the enzyme.

1. Defined the substrate transport and inhibition mechanisms of the anion exchanger Pendrin using high-resolution cryo-EM structures (~2.5–2.8 Å) captured with multiple substrates. Identified the inhibitor binding site through a Pendrin–niflumic acid complex, providing structural insight into inhibition. Validated transport function using proteoliposome assays with radiolabeled (¹⁴C) bicarbonate. 2. Elucidated the molecular mechanism of substrate recognition and catalysis in cholinephosphotransferase-1 (CHPT1) through integrated structural and biochemical approaches. Determined substrate-bound cryo-EM structures and developed an enzyme-coupled assay to quantify activity via phosphate (Pi) production using malachite green detection.

1. Elucidated the proton-coupled sulfate transport mechanism in a plant sulfate transporter by determining high-resolution cryo-EM structures and validating function through liposome-based transport assays, establishing the basis of proton-driven substrate translocation. 2. Investigated the electron transfer mechanism of six-transmembrane epithelial antigen of the prostate 2 (STEAP2) using cryo-EM. Resolved cofactor-bound (heme and FAD) structures, revealing a putative electron transfer pathway and providing mechanistic insight into redox activity.

Responsible for the construction of mutation library of MmRS, and the screening and incorporation of visible light-reactive unnatural amino acids.

1. Determined the 2.3 Å X-ray crystal structure of an algal vitamin transporter and characterized its transport mechanism using proteoliposome-based assays, providing structural and functional insight into substrate translocation. 2. Elucidated the mechanism of substrate recognition and catalysis in human diacylglycerol O-acyltransferase 1 (DGAT1) by solving a ~3.0 Å cryo-EM structure. Developed and implemented an enzyme-coupled assay to quantify activity, enabling integrated structural and functional analysis of lipid biosynthesis.

unnatural amino acid application in chemical biology