Peilong Lu, Ph. D.
Dr. Lu received his bachelor’s degree in Biological Science in 2009, from University of Science and Technology of China (USTC). Then he pursued his doctoral degree in Prof. Yigong Shi’s lab at Tsinghua University until 2014. In 2015, he joined Prof. David Baker’s lab at University of Washington for postdoctoral training, awarded Sackler Fellowship. With his Ph.D. research focused on the structural and biochemical studies of transmembrane proteins, Dr. Lu accurately designed several multipass transmembrane proteins, as a postdoc, paving the way for the design of multispan membrane proteins with new functions. He has published 14 research papers in journals including Science, Nature, PNAS and Cell Research.
Lu lab will mainly focus on computationally design of new generations of functional multipass transmembrane proteins, and design of small proteins targeting disease-related membrane proteins. His group proposes to overcome several key challenges. (i) Use computational protein design methods to develop new generation of transmembrane nanopores and design ion channels with specific selectivity, from scratch. (ii) Extend effort to design transmembrane proteins with cavities that could bind small molecules. One example is to design receptors that could oligomerize and signal upon ligand binding. (iii) Combine computational design effort with massively parallel gene synthesis followed by high-throughput screen to make de novo designed binders for disease-related membrane proteins. Seamless interaction of computational protein design, high-throughput screening, channel activity studies, ligand binding efficacy studies, membrane protein expression and structure determination in Lu lab will provide insights into principles of transmembrane protein design.
1. Lu P, Min D, DiMaio F, Wei KY, Vahey MD, Boyken SE, Chen Z, Fallas JA, Ueda G, Sheffler W, Mulligan VK, Xu W, Bowie JU, Baker D. Accurate computational design of multipass transmembrane proteins. Science. 2018; 359(6379):1042-1046.
2. Chen Z, Boyken SE, Jia M, Busch F, Flores-Solis D, Bick MJ, Lu P, VanAernum ZL, Sahasrabuddhe A, Langan RA, Bermeo S, Brunette TJ, Mulligan VK, Carter LP, DiMaio F, Sgourakis NG, Wysocki VH, Baker D. Programmable design of orthogonal protein heterodimers. Nature. 2018 Dec 19.
3. Ma D, Wang Z, Merrikh CN, Lang KS, Lu P, Li X, Merrikh H, Rao Z, Xu W. Crystal structure of a membrane-bound O-acyltransferase. Nature. 2018 Oct;562(7726):286-290.
4. Jiang D, Gamal El-Din TM, Ing C, Lu P, Pomès R, Zheng N, Catterall WA. Structural basis for gating pore current in periodic paralysis. Nature. 2018 May;557(7706):590-594.
5. Bai X*, Yan C*, Yang G*, Lu P, Ma D, Sun L, Zhou R, Sheres S, Shi Y. An atomic structure of human γ-secretase. Nature. 2015; 525(7568):212-217.
6. Lu P*, Ma D*, Yan C, Gong X, Du M, Shi Y. Structure and mechanism of a eukaryotic transmembrane ascorbate-dependent oxidoreductase. PNAS 2014; 111(5):1813-8.
7. Lu P*, Bai X*, Ma D*, Xie T, Yan C, Sun L, Yang G, Zhao Y, Zhou R, Sheres S, Shi Y. Three-dimensional structure of human γ-secretase. Nature. 2014; 512(7513):166-70.
8. Xie T*, Yan C*, Zhou R, Zhao Y, Sun L, Yang G, Lu P, Ma D, Shi Y. Crystal structure of the γ-secretase component nicastrin. PNAS 2014 Sep 16;111(37):13349-54.
9. Lu P*, Ma D*, Chen Y, Guo Y, Chen GQ, Deng H, Shi Y. L-glutamine provides acid resistance for Escherichia coli through enzymatic release of ammonia. Cell Res. 2013; 23(5):635-44.
10. Ma D*, Lu P*, Shi Y. Substrate selectivity of the acid-activated glutamate/γ-aminobutyric acid (GABA) antiporter GadC from Escherichia coli. J Biol Chem. 2013; 288 (21):15148-53.
11. Lu P*, Lu G*, Yan C, Wang L, Li W, Yin P. Structure of the mRNA splicing complex component Cwc2: insights into RNA recognition. Biochem J. 2012; 441(2):591-7.
12. Ma D, Lu P, Yan C, Fan C, Yin P, Wang J, Shi Y. Structure and mechanism of a glutamate-GABA antiporter. Nature. 2012; 483(7391):632-6.
13. Huang W*, Choi W*, Hu W, Mi N, Guo Q, Ma M, Liu M, Tian Y, Lu P, Wang FL, Deng H, Liu L, Gao N, Yu L, Shi Y. Crystal structure and biochemical analyses reveal Beclin 1 as a novel membrane binding protein. Cell Res. 2012; 22(3):473-89.
14. Wang Y*, Huang Y*, Wang J, Cheng C, Huang W, Lu P, Xu YN, Wang P, Yan N, Shi Y. Structure of the formate transporter FocA reveals a pentameric aquaporin-like channel. Nature. 2009; 462(7272):467-72.
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