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Nat Commun. 2019 May 30;10(1):2370. doi: 10.1038/s41467-019-10345-3.

Curvature induction and membrane remodeling by FAM134B reticulon homology domain assist selective ER-phagy.

Author information

1
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max-von-Laue Straße 3, 60438, Frankfurt am Main, Germany.
2
Institute of Biochemistry II, School of Medicine, Goethe University Frankfurt, Theoder-Stern-Kai 7, 60590, Frankfurt am Main, Germany.
3
Buchmann Institute of Molecular Life Sciences, Goethe University Frankfurt, Max-von-Laue Straße 15, 60438, Frankfurt am Main, Germany.
4
Fraunhofer Institute for Molecular Biology and Applied Ecology, Division for Translational Medicine and Pharmacology, Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany.
5
Max Planck Institute of Biophysics, Max-von-Laue Straße 3, 60438, Frankfurt am Main, Germany.
6
Institute of Biochemistry II, School of Medicine, Goethe University Frankfurt, Theoder-Stern-Kai 7, 60590, Frankfurt am Main, Germany. dikic@biochem2.uni-frankfurt.de.
7
Buchmann Institute of Molecular Life Sciences, Goethe University Frankfurt, Max-von-Laue Straße 15, 60438, Frankfurt am Main, Germany. dikic@biochem2.uni-frankfurt.de.
8
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max-von-Laue Straße 3, 60438, Frankfurt am Main, Germany. gerhard.hummer@biophys.mpg.de.
9
Institute for Biophysics, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany. gerhard.hummer@biophys.mpg.de.

Abstract

FAM134B/RETREG1 is a selective ER-phagy receptor that regulates the size and shape of the endoplasmic reticulum. The structure of its reticulon-homology domain (RHD), an element shared with other ER-shaping proteins, and the mechanism of membrane shaping remain poorly understood. Using molecular modeling and molecular dynamics (MD) simulations, we assemble a structural model for the RHD of FAM134B. Through MD simulations of FAM134B in flat and curved membranes, we relate the dynamic RHD structure with its two wedge-shaped transmembrane helical hairpins and two amphipathic helices to FAM134B functions in membrane-curvature induction and curvature-mediated protein sorting. FAM134B clustering, as expected to occur in autophagic puncta, amplifies the membrane-shaping effects. Electron microscopy of in vitro liposome remodeling experiments support the membrane remodeling functions of the different RHD structural elements. Disruption of the RHD structure affects selective autophagy flux and leads to disease states.

PMID:
31147549
PMCID:
PMC6542808
DOI:
10.1038/s41467-019-10345-3
[Indexed for MEDLINE]
Free PMC Article

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