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8gu7

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Selective targeting of the Beclin 2-Atg14L coiled coil complex by stapled peptides promotes autophagy and endolysosomal trafficking of GPCRs

Structural highlights

8gu7 is a 4 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

BAKOR_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 PubMed

AMBRA1 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

↑ Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, Chait BT, Heintz N, Yue Z. Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex. Nat Cell Biol. 2009 Apr;11(4):468-76. doi: 10.1038/ncb1854. Epub 2009 Mar 8. PMID:19270693 doi:http://dx.doi.org/10.1038/ncb1854
↑ Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T, Kurotori N, Maejima I, Shirahama-Noda K, Ichimura T, Isobe T, Akira S, Noda T, Yoshimori T. Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat Cell Biol. 2009 Apr;11(4):385-96. doi: 10.1038/ncb1846. Epub 2009 Mar 8. PMID:19270696 doi:http://dx.doi.org/10.1038/ncb1846
↑ Xiong X, Tao R, DePinho RA, Dong XC. The autophagy-related gene 14 (Atg14) is regulated by forkhead box O transcription factors and circadian rhythms and plays a critical role in hepatic autophagy and lipid metabolism. J Biol Chem. 2012 Nov 9;287(46):39107-14. PMID:22992773 doi:10.1074/jbc.M112.412569
↑ Kim J, Kim YC, Fang C, Russell RC, Kim JH, Fan W, Liu R, Zhong Q, Guan KL. Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. Cell. 2013 Jan 17;152(1-2):290-303. PMID:23332761 doi:10.1016/j.cell.2012.12.016
↑ 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. The potent BECN2-ATG14 coiled-coil interaction is selectively critical for endolysosomal degradation of GPRASP1/GASP1-associated GPCRs. Autophagy. 2023 Jul 13:1-15. PMID:37409929 doi:10.1080/15548627.2023.2233872