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Molecular determinants regulating selective binding of autophagy adapters and receptors to ATG8 proteins

DOI: 10.1038/s41467-019-10059-6 DOI Help

Authors: Martina Wirth (The Francis Crick Institute) , Wenxin Zhang (The Francis Crick Institute) , Minoo Razi (The Francis Crick Institute) , Lynet Nyoni (The Francis Crick Institute (Midland Road)) , Dhira Joshi (The Francis Crick Institute) , Nicola O’reilly (The Francis Crick Institute) , Terje Johansen (University of Tromsø – The Arctic University of Norway) , Sharon A. Tooze (The Francis Crick Institute) , Stephane Mouilleron (The Francis Crick Institute)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 10

State: Published (Approved)
Published: May 2019
Diamond Proposal Number(s): 13775

Open Access Open Access

Abstract: Autophagy is an essential recycling and quality control pathway. Mammalian ATG8 proteins drive autophagosome formation and selective removal of protein aggregates and organelles by recruiting autophagy receptors and adaptors that contain a LC3-interacting region (LIR) motif. LIR motifs can be highly selective for ATG8 subfamily proteins (LC3s/GABARAPs), however the molecular determinants regulating these selective interactions remain elusive. Here we show that residues within the core LIR motif and adjacent C-terminal region as well as ATG8 subfamily-specific residues in the LIR docking site are critical for binding of receptors and adaptors to GABARAPs. Moreover, rendering GABARAP more LC3B-like impairs autophagy receptor degradation. Modulating LIR binding specificity of the centriolar satellite protein PCM1, implicated in autophagy and centrosomal function, alters its dynamics in cells. Our data provides new mechanistic insight into how selective binding of LIR motifs to GABARAPs is achieved, and elucidate the overlapping and distinct functions of ATG8 subfamily proteins.

Subject Areas: Biology and Bio-materials


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography

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s41467-019-10059-6.pdf