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. 2021 Feb 1;10:619727. doi: 10.3389/fonc.2020.619727

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Copyright © 2021 Cerda-Troncoso, Varas-Godoy and Burgos

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Domain architecture of mammalian autophagy receptors and relevant interactions. (A) p62: N-terminal region Phox-BEM1 domain (PB1) mediates p62 homodimerization or its heterodimerization with NBR1; ZZ-type zinc finger domain recognizes N-terminal argenylated substrates (Nt-Arg); nuclear localization signals (NLS1 and NLS2); tumor necrosis factor (TNF) associated receptor-6 (TRAF6) binding (TB) domain; export motif (NES); LC3-interacting region (LIR) motifs mediate the interaction with all Atg8s; KEAP1-interacting region (KIR) binding with KEAP1; and ubiquitin-associated (UBA) domain recognizes mono and poly-ubiquitylated (Mono-Ub and Poly-Ub) substrates. (B) NBR1: PB1 mediates interaction with p62 and itself; ZZ-type Zink finger, Coiled-coil-1 (CC-1) mediates self-oligomerization, four tryptophan (FW); LIR-2 motif; CC-2 domain; LIR-1 motif, binding to Atgs8 proteins more functional that LIR-2; and UBA domain recognizes mono-Ub and poly-Ub substrates. (C) NDP52: skeletal muscle and kidney-enriched inositol phosphatase carboxyl homology domain (SKICH); LC3C-specific LC3-interacting region (CLIR) mediates selective and strong binding to LC3C; Coiled-coil (CC) domain participates in its homodimerization; Galectin-8 binding region (GalBi) mediates the interaction to Galectin-8 in the context xenophay and lysophagy; and ubiquitin-binding zinc finger (UBZ) domain binds to mono-Ub or poly-Ub. (D) OPTN: three Coiled-coil domains are found (CC-1, CC-2, and CC-3). CC-1 domain promotes the formation of a hetero-tetramer complex between OPTN and serine/threonine TANK-binding kinase 1 (TBK1). CC-3 domain mediates the homodimerization of OPTN; a leucine zipper (LZ) domain; LIR motif binds to all members of Atg8s family; ubiquitin-binding domain of ABIN proteins and NEMO (UBAN) binds to methionine1 (Met1)-linked linear polyubiquitin (Met1-l-polyUb) of ubiquitylated cargos; and zinc finger (ZF) domain.