Published 2021
| Version v1
Journal article
Nanoscale architecture of a VAP-A-OSBP tethering complex at membrane contact sites
Contributors
Others:
- Laboratoire Physico-Chimie Curie [Institut Curie] (PCC) ; Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
- Institut de pharmacologie moléculaire et cellulaire (IPMC) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- University of Basel (Unibas)
Description
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 MCS with two membranes and a pair of tethering proteins suitable for cryo-tomography analysis. It includes VAP-A, an ER transmembrane protein interacting with a myriad of cytosolic proteins, and oxysterol-binding protein (OSBP), a lipid transfer protein that transports cholesterol from the ER to the trans Golgi network. We show that VAP-A is a highly flexible protein, allowing formation of MCS of variable intermembrane distance. The tethering part of OSBP contains a central, dimeric, and helical T-shape region. We propose that the molecular flexibility of VAP-A enables the recruitment of partners of different sizes within MCS of adjustable thickness, whereas the T geometry of the OSBP dimer facilitates the movement of the two lipid-transfer domains between membranes.
Abstract
International audienceAdditional details
Identifiers
- URL
- https://hal.sorbonne-universite.fr/hal-03256855
- URN
- urn:oai:HAL:hal-03256855v1
Origin repository
- Origin repository
- UNICA