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EM methods for biological discovery

Lipopolysaccharide (LPS) transport driven by ABC transporters

: Antibiotic resistance has become a global health threat. Gram-negative bacteria are among the most difficult pathogen to combat, mainly due to their unique “outer membrane” which prevents most antibiotics from entering the cells. Lipopolysaccharide (LPS) is the major component of the outer membrane, and LPS molecules form a tightly packed barrier to exclude many antibiotics and detergents. Understanding and targeting LPS biosynthesis are crucial for developing novel antibiotics to break through the outer membrane and kill Gram-negative bacteria. Before being assembled in the outer membrane, LPS has to travel across the inner membrane, periplasm and outer member. This remarkable journey is powered by two ATP-binding cassette (ABC) transporters: MsbA and LptB2FGC. We have used single-particle cryo-EM and functional assays to reveal the mechanisms of these fascinating molecular machines.

Read our recently published articles:

Read our review article in Current Opinion in Structural Biology:

High-resolution views of lipopolysaccharide translocation driven by ABC transporters MsbA and LptB2FGC

: Structural Basis of Protein-Lipid Interaction

The research interests of our group focus on understanding the structure and function of membrane proteins such as transporters and ion channels. One particular interest is to reveal the mechanisms of how proteins sense, move and convert specific lipid molecules. This will be achieved by obtaining high-resolution structures of lipid-interacting proteins, and by studying the dynamic protein conformations in native membrane environment.

: Single-Particle Cryo-Electron Microscopy (cryo-EM)

Cryo-EM is a rapidly advancing research area, powered by the knowledge of biology, physics, material science and computation. Single-particle cryo-EM is a 'rising star' in structural biology, providing remarkably versatile and powerful tools to study the structure and function of biological macromolecules. Single-particle cryo-EM has achieved near-atomic resolution for biological samples ranging from large icosahedral viruses (~100 MDa) to relatively small membrane ion channel (~300 kDa). Compared to more traditional methods such as X-ray crystallography and NMR spectroscopy, cryo-EM demonstrates a number of important advantages, such as small amount of sample required for EM analysis, flexibility in studying different functional states, and computational sorting of mixed conformations.