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

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Item Type:Article
Title:Curvature induction and membrane remodeling by FAM134B reticulon homology domain assist selective ER-phagy
Creators Name:Bhaskara, R.M. and Grumati, P. and Garcia-Pardo, J. and Kalayil, S. and Covarrubias-Pinto, A. and Chen, W. and Kudryashev, M. and Dikic, I. and Hummer, G.
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.
Keywords:Autophagy, Cell Membrane, Electron Microscopy, Endoplasmic Reticulum, Intracellular Signaling Peptides and Proteins, Liposomes, Membrane Proteins, Molecular Dynamics Simulation, Molecular Models, Neoplasm Proteins, Organelle Shape, Protein Domains, Protein Transport, Tumor Cell Line
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:2370
Date:30 May 2019
Official Publication:https://doi.org/10.1038/s41467-019-10345-3
PubMed:View item in PubMed

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