Erhu Cao
Associate Professor of Biochemistry
Ion Channels, Receptors, Transporters, Structural Biology, cryo-EM, Renal Disease
Molecular Biology Program
Biological Chemistry Program
Education
B.S. Huazhong Agricultural University
Ph.D. Albert Einstein College of Medicine
Research
We are broadly interested in understanding atomic-sale mechanisms of how membrane proteins function under normal and diseased states. Membrane proteins play critical roles in nearly every aspect of physiological processes that encompass relaying signals between cells, transporting small molecules and ions across the membrane and catalyzing vital enzymatic reactions. Importantly, membrane proteins constitute ~60% of targets of currently approved drugs and in-depth knowledge about their inner workings is needed to inform the development of novel and effective therapeutic strategies for treating various human diseases. We employ a multidisciplinary approach that includes molecular biology, protein biochemistry, pharmacology, ion channel electrophysiological (patch clamp recording), X-ray crystallography, and single-particle electron cryo-microscopy.
References
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Ha K, Nobuhara M, Wang Q, Walker RV, Qian F, Schartner C, Cao E, Delling M. The heteromeric PC-1/PC-2 polycystin complex is activated by the PC-1 N-terminus. Elife. 2020 Nov 9;9:e60684.
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Vien TN, Wang J, Ng LCT, Cao E, DeCaen P. Molecular dysregulation of ciliary polycystin-2 channels caused by variants in the TOP domain. Proc Natl Acad Sci U S A. 2020 May 12;117(19):10329-10338.
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Cao E. Structural Mechanisms of Transient Receptor Potential Ion Channels. J Gen Physiol. 2020 Mar 2;152(3).
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Yang X, Wang Q, Cao E. Structure of the human cation–chloride cotransporter NKCC1 determined by single-particle electron cryo-microscopy. Nat Commun. 2020 Feb 21;11(1):1016.
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Zheng W, Yang X, Hu R, Cai R, Hofmann L, Wang Z, Hu Q, Liu X, Bulkey D, Yu Y, Tang J, Flockerzi V, Cao Y, Cao E, Chen X. Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels. Nature Communications. 2018; 9:2302.
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Shen PS, Yang X, DeCaen PG, Liu X, Bulkley D, Clapham DE, Cao E. The Structure of the Polycystic Kidney Disease Channel PKD2 in Lipid Nanodiscs. Cell. 2016 Oct 20; 167(3): 763-773.
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Gao Y, Cao E, Julius D, Cheng Y. TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action. Nature. 2016 Jun 16; 534(7607): 347-51.
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Liao M, Cao E, Julius D, Cheng Y. Single particle electron cryo-microscopy of a mammalian ion channel. Review. Curr Opin Struct Biol. 2014 Aug; 27: 1-7.
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Cao E, Liao M, Cheng Y, Julius D. TRPV1 structures in distinct conformations reveal activation mechanisms. Nature. 2013 Dec 5; 504(7478): 113-8.
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Liao M, Cao E, Julius D, Cheng Y. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature. 2013 Dec 5; 504(7478): 107-12.
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Cao E, Cordero-Morales JF, Liu B, Qin F, Julius D. TRPV1 channels are intrinsically heat sensitive and negatively regulated by phosphoinositide lipids. Neuron. 2013 Feb 20; 77(4): 667-79.
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Lázár-Molnár E, Yan Q, Cao E, Ramagopal U, Nathenson SG, Almo SC. Crystal structure of the complex between programmed death-1 (PD-1) and its ligand PD-L2. Proc Natl Acad Sci U S A. 2008 Jul 29; 105(30): 10483-8.
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Yan Q, Malashkevich VN, Fedorov A, Fedorov E, Cao E, Lary JW, Cole JL, Nathenson SG, Almo SC. Structure of CD84 provides insight into SLAM family function. Proc Natl Acad Sci U S A. 2007 Jun 19; 104(25): 10583-8.
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Cao E, Zang X, Ramagopal UA, Mukhopadhaya A, Fedorov A, Fedorov E, Zencheck WD, Lary JW, Cole JL, Deng H, Xiao H, Dilorenzo TP, Allison JP, Nathenson SG, Almo SC. T cell immunoglobulin mucin-3 crystal structure reveals a galectin-9-independent ligand-binding surface. Immunity. 2007 Mar; 26(3): 311-21.
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Cao E, Ramagopal UA, Fedorov A, Fedorov E, Yan Q, Lary JW, Cole JL, Nathenson SG, Almo SC. NTB-A receptor crystal structure: insights into homophilic interactions in the signaling lymphocytic activation molecule receptor family. Immunity. 2006 Oct; 25(4): 559-70.
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Yu Y, Bai L, Minagawa K, Jian X, Li L, Li J, Chen S, Cao E, Mahmud T, Floss HG, Zhou X, Deng Z. Gene cluster responsible for validamycin biosynthesis in Streptomyces hygroscopicus subsp. jinggangensis 5008. Appl Environ Microbiol. 2005 Sep; 71(9): 5066-76.
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Zhang X, Schwartz JC, Guo X, Bhatia S, Cao E, Lorenz M, Cammer M, Chen L, Zhang ZY, Edidin MA, Nathenson SG, Almo SC. Structural and functional analysis of the costimulatory receptor programmed death-1. Immunity. 2004 Mar; 20(3): 337-47. Erratum in: Immunity. 2004 May; 20(5): 651.