Membrane protein act as a gate keeper or a diode in the cell membranes, which plays an important role in maintaining physiological processes in response to environmental changes. Our lab interests are the structures and functions of membrane proteins, particularly in the context of membrane bilayers. We are tackling the fundamental questions about:

Aquaporin-0 (AQP0) with membrane lipids.

Our lab use cryogenic electron microscopy (cryo-EM) method combined with other biochemical and biophysical approaches, such as lipid nanodiscs technique, to probe the membrane protein structure in its native-like environment. We are also capable of using electron crystallography (two-dimensional (2D) crystal specimens or helical objects) or single-particle cryo-EM to study the interaction of protein with membrane lipids at high resolution. We initially focus on the receptor complex structure of the inhibitory signaling of axonal regeneration.

Negatively-stained MloK1 revealed by electron crystallography and single-particle reconstruction.

When neuron encounters an axonal injury, the oligodendrocyte expresses the myelin-associated inhibitors (MAI) that are transported to the plasma membranes, and the exposed MAIs will acutely inhibit the axonal regeneration of the injured neuron to maintain its plasticity. These MAIs are also correlated with immune actions. To understand the structural relationship and the interactions between these MAIs and their receptors help us develop a medical strategy to treat the diseases related to the axonal regeneration.

Arizona State University (ASU) has a long history of international leadership in the field of electron microscopy. The Center for High Resolution Electron Microscopy, established as a National Science Foundation (NSF) Regional Center by Professor John M. Cowley in 1980, currently houses three aberration-corrected transmission electron microscopes (TEMs) and one Titan Krios TEM. The existing resources for structural biology studies on the campus include the Magnetic Resonance Research Center (MRRC), the College of Liberal Arts and Sciences (CLAS) Electron Paramagnetic Resonance (EPR), and the CLAS-EM Facility. Additionally, ASU has pioneering research groups in the field of X-ray free electron lasers (XFEL) and femtosecond nanocrystallography. The Center for Applied Structural Discovery (CASD) at the Biodesign Institute is currently building the world’s first high energy compact Free Electron Laser in collaboration with Massachusetts Institute of Technology, which will be hosted in the basement of the new Biodesign C building.

Single-particle cryo-EM structure of an F-type ATP synthase (Left: F1 density; Right: transmembrane c-ring).

The most exciting news in the cryo-EM field in recent years is the invention of the direct electron detector (DED) camera. This new detector enables us to explore more possibilities to improve the quality of the structural information of the biological molecules. What’s more, the dose fragmentation of the camera gives us an additional data dimensionality. In addition to the membrane protein studies, we are also interested in taking this advantage and improving the cryo-EM method to increase the productivity in the field of structural biology.

(A) Power spectrum and (B) IQ-plot of the AQP0/cholesterol 2D crystal image with its projectionn reconstruction in (C) grey and (D) contour representations.