Our lab focuses on dissecting the mechanisms of macromolecule-driven membrane shaping and remodeling across cellular, tissue, and organismal scales through direct visualization.
Bridge-like lipid transfer proteins (BLTPs) are a specialized group of proteins with a hydrophobic channel that runs along their entire length. This unique structure allows them to transport lipids in vitro and likely in vivo. They are proposed to function in membrane remodeling, and are essential for cellular function and brain health. However, their structure, function and regulation within cells remain poorly understood.
Our main approach is cellular cryo-ET, which allows us to directly visualize BLTPs and their associated subcellular structures at molecular resolution within lifelike cells.
We previously visualized a member of BLTP family protein, VPS13C, in its natural context within cells, contacts between the endoplasmic reticulum (ER) and lysosomes. Its in situ architecture at these contacts is consistent with its functioning as a bridge that allows lipids to slide between closely apposed bilayers along a hydrophobic groove that runs along its entire length (Cai et al., 2022).
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