Bridge-like lipid transfer proteins 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. However, their precise function within cells remains unclear. We aim to investigate the in situ structural mechanism of BLTPs using the powerful cryo-electron tomography (cryo-ET) technique.
We visualize a member of this family, 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. PNAS, 2022)
To visualize BLTPs in situ, we employ state-of-the-art technology cellular cryo-electron tomography, in combination with cryo-focused ion beam, cryo-correlated light-electron microscopy, and volume-EM. These advanced methods allow us to directly visualize BLTPs and their associated subcellular structures at molecular resolution within lifelike cells.
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