Zhe Zhang

 

Email：zzhang01（at）pku（dot）edu（dot）cn

 

Research Area:

 

Membrane proteins constitute about 1/3 of the total proteins in living organisms. Owing to their essential roles in a variety of fundamental biological processes, about 60% of approved drugs target the membrane proteins. Therefore, scientific research on membrane proteins not only has its biological significance, but also plays an important role in the drug development.

 

Our lab focuses on the mechanistic study of important membrane proteins, especially the disease-related ones, aiming to illustrate their functional mechanisms as well as to guide the downstream drug development. We mainly carry out structural study using single-particle Cryo-EM and X-ray crystallography. In order to thoroughly understand our scientific questions, we also combine biochemical, cell biology, and all the other necessary techniques.

  

Membrane proteins can be mainly divided into four categories according to their different functions: channels, receptors, transporters, and enzymes. Our lab is particularly interested in two classes of them: transporters and receptors. In the short term, we will first focus on the study of solute carrier (SLC) transporter family. SLC transporters are a kind of secondary transporters, and they are the second largest membrane protein family after GPCR (G-protein coupled receptors). Human has more than 400 SLC transporters which are divided into over 50 subfamilies. SLC transporters passively transport their substrates across the cell membrane down their concentration gradients, or they can transport one substrate against its chemical gradient using the energy from transporting another substrate. The substrates for different SLC members vary greatly, ranging from inorganic ions to neurotransmitters, nutrients, and drugs. In the long term, we will also study different families of membrane receptors, including receptor tyrosine kinases (RTKs) and Notch receptors.

 

 

Selected Publications：

 

1.    Fangyu Liu*, Zhe Zhang*, Anat Levit, Jesper Levring, Kouki K. Touhara, Brian K. Shoichet, and Jue Chen$; Structural identification of a hotspot on CFTR for potentiation; Science; 2019,364(6446): 1184-1188. (doi: 10.1126/science.aaw7611) (*co-first author)

2.    Zhe Zhang*, Fangyu Liu*, and Jue Chen$; Molecular structure of the ATP-bound, phosphorylated human CFTR; Proc. Natl. Acad. Sci. USA; 2018, 115(50): 12757-12762. (doi: 10.1073/pnas.1815287115) (*co-first author)

 3.    Zhe Zhang* $, Bal a´zs Tóth*, Andras Szollosi, Jue Chen, and L a´szló Csan a´dy$; Structure of a TRPM2 channel in complex with Ca2+ explains unique gating regulation; eLife; 2018, 7: e36409. (doi: 10.7554/eLife.36409) (*co-first author, $ corresponding author)

 4.    Zhe Zhang, Fangyu Liu, and Jue Chen$; Conformational changes of CFTR upon phosphorylation and ATP binding; Cell; 2017, 170(3): 483-491.e8. (doi: 10.1016/j.cell.2017.06.041)

 5.    Fangyu Liu*, Zhe Zhang*, L a´szló Csan a´dy, David C Gadsby, and Jue Chen$; Molecular structure of the human CFTR ion channel; Cell; 2017, 169(1): 85-95.e8. (doi: 10.1016/j.cell.2017.02.024) (*co-first author)

 6.   Zhe Zhang, and Jue Chen$; Atomic structure of the cystic fibrosis transmembrane conductance regulator; Cell; 2016, 167(6): 1586-1597.e9. (doi: 10.1016/j.cell.2016.11.014)

 7.    Zhe Zhang*, ShanshanWang*, Tong Shen, Jiangye Chen, and Jianping Ding$; Crystal structure of the Rab9A-RUTBC2 RBD complex reveals the molecular basis for the binding specificity of Rab9A with RUTBC2; Structure; 2014, 22 (10): 1408-1422. (doi: 10.1016/j.str.2014.08.005) (*co-first author)

 8.    Zhe Zhang, Tianlong Zhang, Shanshan Wang, Zhou Gong, Chun Tang, Jiangye Chen, and Jianping Ding$; Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5; eLife; 2014, 3: e02687. (doi: 10.7554/eLife.02687)