Maofu Liao

Maofu Liao

Associate Professor
Department of Cell Biology, Harvard Medical School
Maofu Liao

We use high-resolution cryo-electron microscopy (cryo-EM) to study the structure and function of membrane proteins and DNA-protein machines.

The research interests of Liao lab focus on using high-resolution cryo-electron microscopy (cryo-EM) to understand the structure, function and regulation of membrane proteins and other molecular machines. The goal is to uncover fundamental mechanisms of protein machineries, and also push the development of new methodology in cryo-EM.

Single-particle cryo-EM emerges as a transformative approach for structural biology, mainly driven by several technical breakthroughs in recent years. Traditional X-ray and electron crystallographic methods for solving structures require the formation of well-ordered crystals, which often becomes a roadblock for structural analysis. In contrast, cryo-EM directly images the macromolecules frozen in buffer solution, and thus circumvents the need of crystallization. Cryo-EM has a number of other important advantages, such as small amounts of sample needed for EM analysis, suitability for studying different functional states, and computational sorting of mixed conformations from a single sample. Using single-particle cryo-EM, my recent work on TRPV1 ion channel (Nature 504, 107&113, '13) generated the very first atomic structure for membrane proteins without forming crystals. My own work and many recent high-resolution cryo-EM structures from other groups have demonstrated the power of this approach not only to determine novel structures but also to provide deep mechanistic insights into the function.

One particular research interest in Liao lab is to reveal how membrane proteins sense, transport and convert specific lipid molecules. This will be achieved by obtaining high-resolution structures of lipid-interacting proteins, and by investigating their conformation dynamics in native membrane environment. The proteins we are studying include Niemann-Pick C1 (NPC1) and ATP binding cassette A1 (ABCA1) that are critical for cholesterol update and efflux, respectively. We aim to obtain cryo-EM reconstructions at near-atomic resolution for these membrane proteins in different functional states, which will enable atomic model building and uncover the detailed mechanisms that underlie whole body lipid homeostasis. Liao lab is also interested in studying other macromolecular complexes that play critical roles in immune response and development, including RAG1-RAG2 complex that mediates V(D)J recombination for generating a highly diverse population of immunoglobulins and T-cell receptors in the vertebrate immune system. Furthermore, Liao lab is also developing new methodologies, which include 1) establishing in vitro reconstitution systems for cryo-EM studies of membrane proteins in native-like lipid bilayer; 2) optimizing automatic acquisition and processing of large EM data sets; 3) developing new computation algorithms for robust and accurate separation of mixed conformations.

Selected Publications:

Heng Ru, Melissa G. Chambers, Tian-Min Fu, Alexander B. Tong, Maofu Liao*, Hao Wu*. (2015) Molecular mechanism of V(D)J recombination from synaptic RAG1-RAG2 complex structures. Cell. 2015 Nov 19;163(5):1138-52.

Maofu Liao*, Erhu Cao*, David Julius and Yifan Cheng. (2013) Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504, 107–112.

Erhu Cao*, Maofu Liao*, Yifan Cheng and David Julius. (2013) TRPV1 structures in distinct conformations reveal activation mechanisms. Nature 504, 113–118.

Daniele Canzio, Maofu Liao, Nariman Naber, Ed Pate, Adam Larson, Shenping Wu, Diana Marina, Jennifer Garcia, Hiten Madhani, Roger Cooke, Peter Schuck, Yifan Cheng, Geeta J. Narlikar. (2013) A conformational switch in HP1 releases auto-inhibition to drive heterochromatin assembly. Nature 496: 377–381.

Contact Information

HMS, Department of Cell Biology
Seeley G. Mudd Building, Room 509
250 Longwood Avenue, Boston, MA 02115

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