6hyn
From Proteopedia
Structure of ATG13 LIR motif bound to GABARAP
Structural highlights
FunctionATG13_HUMAN Autophagy factor required for autophagosome formation and mitophagy. Target of the TOR kinase signaling pathway that regulates autophagy through the control of the phosphorylation status of ATG13 and ULK1, and the regulation of the ATG13-ULK1-RB1CC1 complex. Through its regulation of ULK1 activity, plays a role in the regulation of the kinase activity of mTORC1 and cell proliferation.[1] [2] [3] [4] [5] [6] GBRAP_HUMAN May play a role in intracellular transport of GABA(A) receptors and its interaction with the cytoskeleton. Involved in apoptosis. Involved in autophagy (By similarity).[7] Publication Abstract from PubMedAutophagy 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. Molecular determinants regulating selective binding of autophagy adapters and receptors to ATG8 proteins.,Wirth M, Zhang W, Razi M, Nyoni L, Joshi D, O'Reilly N, Johansen T, Tooze SA, Mouilleron S Nat Commun. 2019 May 3;10(1):2055. doi: 10.1038/s41467-019-10059-6. PMID:31053714[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Johansen T | Joshi D | Mouilleron S | Nyoni L | O'Reilly N | Razi M | Tooze S | Wirth M | Zhang W
