8gu7 | pdb_00008gu7
Selective targeting of the Beclin 2-Atg14L coiled coil complex by stapled peptides promotes autophagy and endolysosomal trafficking of GPCRs
Structural highlights
FunctionBAKOR_MOUSE Required for both basal and inducible autophagy (PubMed:19270696, PubMed:19270693). Determines the localization of the autophagy-specific PI3-kinase complex PI3KC3-C1 (By similarity). Plays a role in autophagosome formation and MAP1LC3/LC3 conjugation to phosphatidylethanolamine (PubMed:19270696, PubMed:19270693). Promotes BECN1 translocation from the trans-Golgi network to autophagosomes (By similarity). Enhances PIK3C3 activity in a BECN1-dependent manner. Essential for the autophagy-dependent phosphorylation of BECN1 (By similarity). Stimulates the phosphorylation of BECN1, but suppresses the phosphorylation of PIK3C3 by AMPK (PubMed:23332761). Binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction to promote autophagosome-endolysosome fusion (By similarity). Modulates the hepatic lipid metabolism (PubMed:22992773).[UniProtKB:Q6ZNE5][1] [2] [3] [4] Publication Abstract from PubMedAMBRA1 autophagy and beclin 1 regulator 1; ATG14 autophagy related 14; ATG5 autophagy related 5; ATG7 autophagy related 7; BECN1 beclin 1; BECN2 beclin 2; CC coiled-coil; CQ chloroquine CNR1/CB1R cannabinoid receptor 1 DAPI 4',6-diamidino-2-phenylindole; dCCD delete CCD; DRD2/D2R dopamine receptor D2 GPRASP1/GASP1 G protein-coupled receptor associated sorting protein 1 GPCR G-protein coupled receptor; ITC isothermal titration calorimetry; IP immunoprecipitation; KD knockdown; KO knockout; MAP1LC3/LC3 microtubule associated protein 1 light chain 3; NRBF2 nuclear receptor binding factor 2; OPRD1/DOR opioid receptor delta 1 PIK3C3/VPS34 phosphatidylinositol 3-kinase catalytic subunit type 3; PIK3R4/VPS15 phosphoinositide-3-kinase regulatory subunit 4; PtdIns3K class III phosphatidylinositol 3-kinase; PtdIns3P phosphatidylinositol-3-phosphate; RUBCN rubicon autophagy regulator; SQSTM1/p62 sequestosome 1; UVRAG UV radiation resistance associated; VPS vacuolar protein sorting; WT wild type. The potent BECN2-ATG14 coiled-coil interaction is selectively critical for endolysosomal degradation of GPRASP1/GASP1-associated GPCRs.,Qiu X, Li N, Yang Q, Wu S, Li X, Pan X, Yamamoto S, Zhang X, Zeng J, Liao J, He C, Wang R, Zhao Y Autophagy. 2023 Jul 13:1-15. doi: 10.1080/15548627.2023.2233872. PMID:37409929[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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