7brt

From Proteopedia

Crystal structure of Sec62 LIR fused to GABARAP

PDB ID 7brt

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Structural highlights

7brt is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.999Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SEC62_HUMAN Mediates post-translational transport of precursor polypeptides across endoplasmic reticulum (ER). Proposed to act as a targeting receptor for small presecretory proteins containing short and apolar signal peptides. Targets and properly positions newly synthesized presecretory proteins into the SEC61 channel-forming translocon complex, triggering channel opening for polypeptide translocation to the ER lumen.^[1] ^[2] 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).^[3]

Publication Abstract from PubMed

The endoplasmic reticulum (ER) is selectively degraded by autophagy (ER-phagy) through proteins called ER-phagy receptors. In Saccharomyces cerevisiae, Atg40 acts as an ER-phagy receptor to sequester ER fragments into autophagosomes by binding Atg8 on forming autophagosomal membranes. During ER-phagy, parts of the ER are morphologically rearranged, fragmented, and loaded into autophagosomes, but the mechanism remains poorly understood. Here we find that Atg40 molecules assemble in the ER membrane concurrently with autophagosome formation via multivalent interaction with Atg8. Atg8-mediated super-assembly of Atg40 generates highly-curved ER regions, depending on its reticulon-like domain, and supports packing of these regions into autophagosomes. Moreover, tight binding of Atg40 to Atg8 is achieved by a short helix C-terminal to the Atg8-family interacting motif, and this feature is also observed for mammalian ER-phagy receptors. Thus, this study significantly advances our understanding of the mechanisms of ER-phagy and also provides insights into organelle fragmentation in selective autophagy of other organelles.

Super-assembly of ER-phagy receptor Atg40 induces local ER remodeling at contacts with forming autophagosomal membranes.,Mochida K, Yamasaki A, Matoba K, Kirisako H, Noda NN, Nakatogawa H Nat Commun. 2020 Jul 3;11(1):3306. doi: 10.1038/s41467-020-17163-y. PMID:32620754^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lang S, Benedix J, Fedeles SV, Schorr S, Schirra C, Schauble N, Jalal C, Greiner M, Hassdenteufel S, Tatzelt J, Kreutzer B, Edelmann L, Krause E, Rettig J, Somlo S, Zimmermann R, Dudek J. Different effects of Sec61alpha, Sec62 and Sec63 depletion on transport of polypeptides into the endoplasmic reticulum of mammalian cells. J Cell Sci. 2012 Apr 15;125(Pt 8):1958-69. doi: 10.1242/jcs.096727. Epub 2012 Feb, 28. PMID:22375059 doi:http://dx.doi.org/10.1242/jcs.096727
↑ Hassdenteufel S, Johnson N, Paton AW, Paton JC, High S, Zimmermann R. Chaperone-Mediated Sec61 Channel Gating during ER Import of Small Precursor Proteins Overcomes Sec61 Inhibitor-Reinforced Energy Barrier. Cell Rep. 2018 May 1;23(5):1373-1386. doi: 10.1016/j.celrep.2018.03.122. PMID:29719251 doi:http://dx.doi.org/10.1016/j.celrep.2018.03.122
↑ Lee JH, Rho SB, Chun T. GABAA receptor-associated protein (GABARAP) induces apoptosis by interacting with DEAD (Asp-Glu-Ala-Asp/His) box polypeptide 47 (DDX 47). Biotechnol Lett. 2005 May;27(9):623-8. PMID:15977068 doi:http://dx.doi.org/10.1007/s10529-005-3628-2
↑ Mochida K, Yamasaki A, Matoba K, Kirisako H, Noda NN, Nakatogawa H. Super-assembly of ER-phagy receptor Atg40 induces local ER remodeling at contacts with forming autophagosomal membranes. Nat Commun. 2020 Jul 3;11(1):3306. doi: 10.1038/s41467-020-17163-y. PMID:32620754 doi:http://dx.doi.org/10.1038/s41467-020-17163-y