Peng Yuan, PhD

Drug discovery

We aim to gain a comprehensive understanding of the physicochemical principles of membrane transport and to establish new foundations for mechanism-based rational therapies.

Structure and function of membrane transport proteins

Selective transport of ions, nutrients, and folded proteins across cell membranes, mediated by membrane transport proteins, is a fundamental biological process. We are interested in understanding molecular mechanisms of membrane transport proteins such as ion channels and transporters that play essential roles in physiology and disease. How do ion channels and transporters recognize their specific substrate ions? How do channels open and close their ion conduction pores in response to environmental cues and cellular stimuli such as chemicals, temperature, membrane voltage and mechanical force? To answer these fundamental questions, my lab uses multidisciplinary approaches including electrophysiology, biochemical and biophysical assays, and structural biology. Dysfunction of these membrane proteins leads to a wide range of diseases, including asthma, hypertension, cancer, heart failure, diabetes and chronic pain. Our goal is to advance our understanding of structure and function of these essential membrane proteins at the atomic level.

Mount J, Maksaev G, Summers BT, Fitzpatrick JA, Yuan P. Structural basis for mechanotransduction in a potassium-dependent mechanosensitive ion channel. Nature communications 2022 Nov; 13(1).

Bitter RM, Oh S, Deng Z, Rahman S, Hite RK, Yuan P. Structure of the Wilson disease copper transporter ATP7B. Science advances 2022 Mar; 8(9).

Ge EJ, Bush AI, Casini A, Cobine PA, Cross JR, DeNicola GM, Dou QP, Franz KJ, Gohil VM, Gupta S, Kaler SG, Lutsenko S, Mittal V, Petris MJ, Polishchuk R, Ralle M, Schilsky ML, Tonks NK, Vahdat LT, Van Aelst L, Xi D, Yuan P, Brady DC, Chang CJ. Connecting copper and cancer: from transition metal signalling to metalloplasia. Nature reviews. Cancer 2022 Feb; 22(2).

Deng Z, Zhao Y, Feng J, Zhang J, Zhao H, Rau MJ, Fitzpatrick JA, Hu H, Yuan P. Cryo-EM structure of a proton-activated chloride channel TMEM206. Science advances 2021 Feb; 7(9).

Deng Z, Maksaev G, Schlegel AM, Zhang J, Rau M, Fitzpatrick JA, Haswell ES, Yuan P. Structural mechanism for gating of a eukaryotic mechanosensitive channel of small conductance. Nature communications 2020 Jul; 11(1).

Deng Z, Maksaev G, Rau M, Xie Z, Hu H, Fitzpatrick JA, Yuan P. Gating of human TRPV3 in a lipid bilayer. Nature structural & molecular biology 2020 Jul; 27(7).

Geng Y, Deng Z, Zhang G, Budelli G, Butler A, Yuan P, Cui J, Salkoff L, Magleby KL. Coupling of Ca and voltage activation in BK channels through the αB helix/voltage sensor interface. Proceedings of the National Academy of Sciences of the United States of America 2020 Jun; 117(25).

Deng Z, He Z, Maksaev G, Bitter RM, Rau M, Fitzpatrick JA, Yuan P. Cryo-EM structures of the ATP release channel pannexin 1. Nature structural & molecular biology 2020 Apr; 27(4).

Ren F, Logeman BL, Zhang X, Liu Y, Thiele DJ, Yuan P. X-ray structures of the high-affinity copper transporter Ctr1. Nature communications 2019 Mar; 10(1).

Omattage NS, Deng Z, Pinkner JS, Dodson KW, Almqvist F, Yuan P, Hultgren SJ. Structural basis for usher activation and intramolecular subunit transfer in P pilus biogenesis in Escherichia coli. Nature microbiology 2018 Dec; 3(12).

Deng Z, Paknejad N, Maksaev G, Sala-Rabanal M, Nichols CG, Hite RK, Yuan P. Cryo-EM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms. Nature structural & molecular biology 2018 Mar; 25(3).

Lee SJ, Ren F, Zangerl-Plessl EM, Heyman S, Stary-Weinzinger A, Yuan P, Nichols CG. Structural basis of control of inward rectifier Kir2 channel gating by bulk anionic phospholipids. The Journal of general physiology 2016 Sep; 148(3).

Hite RK, Yuan P, Li Z, Hsuing Y, Walz T, MacKinnon R. Cryo-electron microscopy structure of the Slo2.2 Na(+)-activated K(+) channel. Nature 2015 Nov; 527(7577).

Leonetti MD, Yuan P, Hsiung Y, Mackinnon R. Functional and structural analysis of the human SLO3 pH- and voltage-gated K+ channel. Proceedings of the National Academy of Sciences of the United States of America 2012 Nov; 109(47).

Yuan P, Leonetti MD, Hsiung Y, MacKinnon R. Open structure of the Ca2+ gating ring in the high-conductance Ca2+-activated K+ channel. Nature 2011 Dec; 481(7379).

Yuan P, Leonetti MD, Pico AR, Hsiung Y, MacKinnon R. Structure of the human BK channel Ca2+-activation apparatus at 3.0 A resolution. Science (New York, N.Y.) 2010 Jul; 329(5988).