Nanoscale architecture of a VAP-A-OSBP tethering complex at membrane contact sites

• DOI: 10.1038/s41467-021-23799-1
• Publication Date: 2021-06-08T10:07:47Z
• Authors: Eugenio de la Mora; Manuela Dezi; Aurélie Di Cicco; Joëlle Bigay; Romain Gautier; John Manzi; Joël Polidori; Daniel Castaño-Díez; Bruno Mesmin; Bruno Antonny; Daniel Lévy
• Keywords: Tethering; Organelle; Membrane contact site

Abstract Membrane contact sites (MCS) are subcellular regions where two organelles appose their membranes to exchange small molecules, including lipids. Structural information on how proteins form MCS is scarce. We designed an in vitro with and a pair of tethering suitable for cryo-tomography analysis. It includes VAP-A, ER transmembrane protein interacting myriad cytosolic proteins, oxysterol-binding (OSBP), lipid transfer that transports cholesterol from the trans Golgi network. show VAP-A highly flexible protein, allowing formation variable intermembrane distance. The part OSBP contains central, dimeric, helical T-shape region. propose molecular flexibility enables recruitment partners different sizes within adjustable thickness, whereas T geometry dimer facilitates movement lipid-transfer domains between membranes.