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4co7

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Crystal structure of human GATE-16

Structural highlights

4co7 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 2Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GBRL2_HUMAN Ubiquitin-like modifier involved in intra-Golgi traffic. Modulates intra-Golgi transport through coupling between NSF activity and SNAREs activation. It first stimulates the ATPase activity of NSF which in turn stimulates the association with GOSR1 (By similarity). Involved in autophagy. Plays a role in mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Whereas LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation.^[1] ^[2]

Publication Abstract from PubMed

Autophagy is a fundamental homeostatic process in eukaryotic organisms, fulfilling essential roles in development and adaptation to stress. Among other factors, formation of autophagosomes critically depends on proteins of the Atg8 (autophagy-related protein 8) family, which are reversibly conjugated to membrane lipids. We have applied X-ray crystallography, nuclear magnetic resonance spectroscopy, and molecular dynamics simulations to study the conformational dynamics of Atg8-type proteins, using GATE-16 (Golgi-associated ATPase enhancer of 16 kDa), also known as GABARAPL2, as a model system. This combination of complementary approaches provides new insight into a structural transition centered on the C-terminus, which is crucial for the biological activity of these proteins.

Conformational Polymorphism in Autophagy-Related Protein GATE-16.,Ma P, Schillinger O, Schwarten M, Lecher J, Hartmann R, Stoldt M, Mohrluder J, Olubiyi O, Strodel B, Willbold D, Weiergraber OH Biochemistry. 2015 Sep 8;54(35):5469-79. doi: 10.1021/acs.biochem.5b00366. Epub, 2015 Aug 26. PMID:26284781^[3]

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

References

↑ Weidberg H, Shvets E, Shpilka T, Shimron F, Shinder V, Elazar Z. LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis. EMBO J. 2010 Jun 2;29(11):1792-802. doi: 10.1038/emboj.2010.74. Epub 2010 Apr 23. PMID:20418806 doi:http://dx.doi.org/10.1038/emboj.2010.74
↑ Zhu Y, Massen S, Terenzio M, Lang V, Chen-Lindner S, Eils R, Novak I, Dikic I, Hamacher-Brady A, Brady NR. Modulation of serines 17 and 24 in the LC3-interacting region of Bnip3 determines pro-survival mitophagy versus apoptosis. J Biol Chem. 2013 Jan 11;288(2):1099-113. doi: 10.1074/jbc.M112.399345. Epub 2012, Dec 3. PMID:23209295 doi:http://dx.doi.org/10.1074/jbc.M112.399345
↑ Ma P, Schillinger O, Schwarten M, Lecher J, Hartmann R, Stoldt M, Mohrluder J, Olubiyi O, Strodel B, Willbold D, Weiergraber OH. Conformational Polymorphism in Autophagy-Related Protein GATE-16. Biochemistry. 2015 Sep 8;54(35):5469-79. doi: 10.1021/acs.biochem.5b00366. Epub, 2015 Aug 26. PMID:26284781 doi:http://dx.doi.org/10.1021/acs.biochem.5b00366