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| | <StructureSection load='6hol' size='340' side='right'caption='[[6hol]], [[Resolution|resolution]] 1.40Å' scene=''> | | <StructureSection load='6hol' size='340' side='right'caption='[[6hol]], [[Resolution|resolution]] 1.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6hol]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HOL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HOL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6hol]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HOL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HOL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.4Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GABARAPL1, GEC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6hol FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hol OCA], [http://pdbe.org/6hol PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hol RCSB], [http://www.ebi.ac.uk/pdbsum/6hol PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hol ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6hol FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hol OCA], [https://pdbe.org/6hol PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hol RCSB], [https://www.ebi.ac.uk/pdbsum/6hol PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hol ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GBRL1_HUMAN GBRL1_HUMAN]] Increases cell-surface expression of kappa-type opioid receptor through facilitating anterograde intracellular trafficking of the receptor. Involved in formation of autophagosomal vacuoles.<ref>PMID:16431922</ref> <ref>PMID:20404487</ref> [[http://www.uniprot.org/uniprot/BAKOR_HUMAN BAKOR_HUMAN]] Required for both basal and inducible autophagy. Determines the localization of the autophagy-specific PI3-kinase complex PI3KC3-C1 (PubMed:18843052, PubMed:19050071). Plays a role in autophagosome formation and MAP1LC3/LC3 conjugation to phosphatidylethanolamine (PubMed:19270696, PubMed:20713597). Promotes BECN1 translocation from the trans-Golgi network to autophagosomes (PubMed:20713597). Enhances PIK3C3 activity in a BECN1-dependent manner. Essential for the autophagy-dependent phosphorylation of BECN1 (PubMed:23878393). Stimulates the phosphorylation of BECN1, but suppresses the phosphorylation PIK3C3 by AMPK (PubMed:23878393). Binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction to promote autophagosome-endolysosome fusion (PubMed:25686604). Modulates the hepatic lipid metabolism (By similarity).[UniProtKB:Q8CDJ3]<ref>PMID:18843052</ref> <ref>PMID:19050071</ref> <ref>PMID:19270696</ref> <ref>PMID:20713597</ref> <ref>PMID:23878393</ref> <ref>PMID:25686604</ref> | + | [https://www.uniprot.org/uniprot/GBRL1_HUMAN GBRL1_HUMAN] Increases cell-surface expression of kappa-type opioid receptor through facilitating anterograde intracellular trafficking of the receptor. Involved in formation of autophagosomal vacuoles.<ref>PMID:16431922</ref> <ref>PMID:20404487</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bhujbal, Z]] | + | [[Category: Bhujbal Z]] |
| - | [[Category: Birgisdottir, A B]] | + | [[Category: Birgisdottir AB]] |
| - | [[Category: Evjen, G]] | + | [[Category: Evjen G]] |
| - | [[Category: Johansen, T]] | + | [[Category: Johansen T]] |
| - | [[Category: Lamark, T]] | + | [[Category: Lamark T]] |
| - | [[Category: Lee, R]] | + | [[Category: Lee R]] |
| - | [[Category: Mouilleron, S]] | + | [[Category: Mouilleron S]] |
| - | [[Category: Reilly, N O]] | + | [[Category: O'Reilly N]] |
| - | [[Category: Sjottem, E]] | + | [[Category: Sjottem E]] |
| - | [[Category: Tooze, S]] | + | [[Category: Tooze S]] |
| - | [[Category: Wirth, M]] | + | [[Category: Wirth M]] |
| - | [[Category: Zhang, W]] | + | [[Category: Zhang W]] |
| - | [[Category: Atg8]]
| + | |
| - | [[Category: Autophagy]]
| + | |
| - | [[Category: Lir]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
GBRL1_HUMAN Increases cell-surface expression of kappa-type opioid receptor through facilitating anterograde intracellular trafficking of the receptor. Involved in formation of autophagosomal vacuoles.[1] [2]
Publication Abstract from PubMed
Autophagosome formation depends on a carefully orchestrated interplay between membrane-associated protein complexes. Initiation of macroautophagy/autophagy is mediated by the ULK1 (unc-51 like autophagy activating kinase 1) protein kinase complex and the autophagy-specific class III phosphatidylinositol 3-kinase complex I (PtdIns3K-C1). The latter contains PIK3C3/VPS34, PIK3R4/VPS15, BECN1/Beclin 1 and ATG14 and phosphorylates phosphatidylinositol to generate phosphatidylinositol 3-phosphate (PtdIns3P). Here, we show that PIK3C3, BECN1 and ATG14 contain functional LIR motifs and interact with the Atg8-family proteins with a preference for GABARAP and GABARAPL1. High resolution crystal structures of the functional LIR motifs of these core components of PtdIns3K-C1were obtained. Variation in hydrophobic pocket 2 (HP2) may explain the specificity for the GABARAP family. Mutation of the LIR motif in ATG14 did not prevent formation of the PtdIns3K-C1 complex, but blocked colocalization with MAP1LC3B/LC3B and impaired mitophagy. The ULK-mediated phosphorylation of S29 in ATG14 was strongly dependent on a functional LIR motif in ATG14. GABARAP-preferring LIR motifs in PIK3C3, BECN1 and ATG14 may, via coincidence detection, contribute to scaffolding of PtdIns3K-C1 on membranes for efficient autophagosome formation.
Members of the autophagy class III phosphatidylinositol 3-kinase complex I interact with GABARAP and GABARAPL1 via LIR motifs.,Birgisdottir AB, Mouilleron S, Bhujabal Z, Wirth M, Sjottem E, Evjen G, Zhang W, Lee R, O'Reilly N, Tooze SA, Lamark T, Johansen T Autophagy. 2019 Feb 15. doi: 10.1080/15548627.2019.1581009. PMID:30767700[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chen C, Li JG, Chen Y, Huang P, Wang Y, Liu-Chen LY. GEC1 interacts with the kappa opioid receptor and enhances expression of the receptor. J Biol Chem. 2006 Mar 24;281(12):7983-93. Epub 2006 Jan 23. PMID:16431922 doi:M509805200
- ↑ Chakrama FZ, Seguin-Py S, Le Grand JN, Fraichard A, Delage-Mourroux R, Despouy G, Perez V, Jouvenot M, Boyer-Guittaut M. GABARAPL1 (GEC1) associates with autophagic vesicles. Autophagy. 2010 May;6(4):495-505. doi: 10.4161/auto.6.4.11819. Epub 2010 May 16. PMID:20404487 doi:10.4161/auto.6.4.11819
- ↑ Birgisdottir AB, Mouilleron S, Bhujabal Z, Wirth M, Sjottem E, Evjen G, Zhang W, Lee R, O'Reilly N, Tooze SA, Lamark T, Johansen T. Members of the autophagy class III phosphatidylinositol 3-kinase complex I interact with GABARAP and GABARAPL1 via LIR motifs. Autophagy. 2019 Feb 15. doi: 10.1080/15548627.2019.1581009. PMID:30767700 doi:http://dx.doi.org/10.1080/15548627.2019.1581009
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