Membrane transport underlies many vital processes in the cell, such as import of nutrients, secretion of proteins and peptides, maintenance of transmembrane ion gradients, and electrical and chemical signaling. Our lab’s research focuses on understanding molecular mechanisms of membrane transport proteins mediating these processes. We mainly use structural, biochemical, and biophysical approaches, particularly cryo-electron microscopy (cryo-EM).
Protein transport across membranes
One of current research focuses in the lab is protein transport across membranes. Many proteins move across membranes to be secreted from cells or to be imported into membrane-bound organelles such as endoplasmic reticulum (ER), peroxisomes, mitochondria, and plastids. These processes constitute fundamental steps in protein and organelle biogenesis, as over 30% of cellular proteins are required to be translocated across a membrane at least once upon their synthesis. Translocation is mediated by classes of membrane protein complexes called protein-conducting channels, the best example of which is the Sec61/SecY complex in eukaryotic ER or prokaryotic plasma membranes. In addition, protein-conducting channels mediate insertion of transmembrane proteins into a lipid bilayer and retro-translocation of damaged proteins back to the cytosol for degradation.
Protein translocation poses many fundamental yet poorly understood biological questions, such as how channels selectively recognize their substrate proteins, how they translocate large polypeptides while maintaining the membrane barrier for small molecules and ions, and how they enable directional polypeptide movement. In our lab, we would like to answer these important questions by biochemical and structural analysis. We aim to visualize structures of these channels in various functional states by cryo-EM and reconstitute the translocation processes with purified components to dissect their operating principles.
Bacterial Protein Translocation Complex SecA-SecY
Schematic (left) and crystal structure visualizing the SecY channel engaged with a polypeptide substrate (right). (from Nature, 2016)
Transport of small molecules by membrane channels and transporters
To be updated.