eprintid: 10075467
rev_number: 21
eprint_status: archive
userid: 608
dir: disk0/10/07/54/67
datestamp: 2019-06-10 14:51:02
lastmod: 2021-10-02 22:03:55
status_changed: 2019-06-10 14:51:02
type: article
metadata_visibility: show
creators_name: Wirth, M
creators_name: Zhang, W
creators_name: Razi, M
creators_name: Nyoni, L
creators_name: Joshi, D
creators_name: O'Reilly, N
creators_name: Johansen, T
creators_name: Tooze, SA
creators_name: Mouilleron, S
title: Molecular determinants regulating selective binding of autophagy adapters and receptors to ATG8 proteins
ispublished: pub
divisions: UCL
divisions: B07
divisions: H19
keywords: Autophagy, X-ray crystallography
note: © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
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.
date: 2019-05-03
date_type: published
publisher: NATURE PUBLISHING GROUP
official_url: https://doi.org/10.1038/s41467-019-10059-6
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_id: 1662475
doi: 10.1038/s41467-019-10059-6
language_elements: English
lyricists_name: Wirth, Martina Barbara
lyricists_id: MWIRT57
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: Nature Communications
volume: 10
article_number: 2055
pages: 18
issn: 2041-1723
citation:        Wirth, M;    Zhang, W;    Razi, M;    Nyoni, L;    Joshi, D;    O'Reilly, N;    Johansen, T;         ... Mouilleron, S; + view all <#>        Wirth, M;  Zhang, W;  Razi, M;  Nyoni, L;  Joshi, D;  O'Reilly, N;  Johansen, T;  Tooze, SA;  Mouilleron, S;   - view fewer <#>    (2019)    Molecular determinants regulating selective binding of autophagy adapters and receptors to ATG8 proteins.                   Nature Communications , 10     , Article 2055.  10.1038/s41467-019-10059-6 <https://doi.org/10.1038/s41467-019-10059-6>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10075467/8/Wirth_Molecular%20determinants%20regulating%20selective%20binding%20of%20autophagy%20adapters%20and%20receptors%20to%20ATG8%20proteins_VoR.pdf