1. An Intrinsically Disordered Region in OSBP Acts as an Entropic Barrier to Control Protein Dynamics and Orientation at Membrane Contact Sites
- Author
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Denisa Jamecna, Daniel Lévy, Manuela Dezi, Bruno Antonny, Joëlle Bigay, Bruno Mesmin, Joël Polidori, Génétique et Ecophysiologie de la qualité des agrumes (GEQA), Institut National de la Recherche Agronomique (INRA), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), 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), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)
- Subjects
Receptors, Steroid ,Golgi Apparatus ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,Endoplasmic Reticulum ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Protein Domains ,Organelle ,Humans ,Molecular Biology ,OSBP ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Organelles ,0303 health sciences ,Protein dynamics ,Cell Membrane ,Cell Biology ,Golgi apparatus ,Lipids ,Membrane contact site ,N-terminus ,Sterols ,Membrane ,Mitochondrial Membranes ,symbols ,Biophysics ,Carrier Proteins ,Plant lipid transfer proteins ,030217 neurology & neurosurgery ,HeLa Cells ,Developmental Biology - Abstract
Summary Lipid transfer proteins (LTPs) acting at membrane contact sites (MCS) between the ER and other organelles contain domains involved in heterotypic (e.g., ER to Golgi) membrane tethering as well as domains involved in lipid transfer. Here, we show that a long ≈90 aa intrinsically unfolded sequence at the N terminus of oxysterol-binding protein (OSBP) controls OSBP orientation and dynamics at MCS. This Gly-Pro-Ala-rich sequence, whose hydrodynamic radius is twice as that of folded domains, prevents the two PH domains of the OSBP dimer from homotypically tethering two Golgi-like membranes and considerably facilitates OSBP in-plane diffusion and recycling at MCS. Although quite distant in sequence, the N terminus of OSBP-related protein-4 (ORP4) has similar effects. We propose that N-terminal sequences of low complexity in ORPs form an entropic barrier that restrains protein orientation, limits protein density, and facilitates protein mobility in the narrow and crowded MCS environment.
- Published
- 2019
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