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| | ==Crystal structure of AnkG LIR/LC3B complex== | | ==Crystal structure of AnkG LIR/LC3B complex== |
| - | <StructureSection load='5yiq' size='340' side='right' caption='[[5yiq]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='5yiq' size='340' side='right'caption='[[5yiq]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5yiq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YIQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YIQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5yiq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YIQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YIQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Map1lc3b, Map1alc3, Map1lc3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Ank3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5yiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yiq OCA], [http://pdbe.org/5yiq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yiq RCSB], [http://www.ebi.ac.uk/pdbsum/5yiq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yiq 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=5yiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yiq OCA], [https://pdbe.org/5yiq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yiq RCSB], [https://www.ebi.ac.uk/pdbsum/5yiq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yiq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MLP3B_MOUSE MLP3B_MOUSE]] Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes). 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. Promotes primary ciliogenesis by removing OFD1 from centriolar satellites via the autophagic pathway.[UniProtKB:Q9GZQ8] [[http://www.uniprot.org/uniprot/ANK3_RAT ANK3_RAT]] Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments. In skeletal muscle, required for costamere localization of DMD and betaDAG1 (By similarity). Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption (By similarity).[UniProtKB:G5E8K5] | + | [https://www.uniprot.org/uniprot/MLP3B_MOUSE MLP3B_MOUSE] Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes). 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. Promotes primary ciliogenesis by removing OFD1 from centriolar satellites via the autophagic pathway.[UniProtKB:Q9GZQ8] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5yiq" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5yiq" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Ankyrin 3D structures|Ankyrin 3D structures]] |
| | + | *[[Microtubule-associated protein 3D structures|Microtubule-associated protein 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | + | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Chen, K]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Li, J]] | + | [[Category: Chen K]] |
| - | [[Category: Wang, C]] | + | [[Category: Li J]] |
| - | [[Category: Yuan, C]] | + | [[Category: Wang C]] |
| - | [[Category: Zhang, H]] | + | [[Category: Yuan C]] |
| - | [[Category: Zhang, M]] | + | [[Category: Zhang H]] |
| - | [[Category: Zheng, H]] | + | [[Category: Zhang M]] |
| - | [[Category: Zhu, R]] | + | [[Category: Zheng H]] |
| - | [[Category: Autophagy]]
| + | [[Category: Zhu R]] |
| - | [[Category: Protein binding]]
| + | |
| Structural highlights
Function
MLP3B_MOUSE Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes). 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. Promotes primary ciliogenesis by removing OFD1 from centriolar satellites via the autophagic pathway.[UniProtKB:Q9GZQ8]
Publication Abstract from PubMed
The mammalian Atg8 family proteins are central drivers of autophagy and contain six members, classified into the LC3 and GABARAP subfamilies. Due to their high sequence similarity and consequent functional overlaps, it is difficult to delineate specific functions of Atg8 proteins in autophagy. Here we discover a super-strong GABARAP-selective inhibitory peptide harbored in 270/480 kDa ankyrin-G and a super-potent pan-Atg8 inhibitory peptide from 440 kDa ankyrin-B. Structural studies elucidate the mechanism governing the Atg8 binding potency and selectivity of the peptides, reveal a general Atg8-binding sequence motif, and allow development of a more GABARAP-selective inhibitory peptide. These peptides effectively blocked autophagy when expressed in cultured cells. Expression of these ankyrin-derived peptides in Caenorhabditis elegans also inhibited autophagy, causing accumulation of the p62 homolog SQST-1, delayed development and shortened life span. Thus, these genetically encodable autophagy inhibitory peptides can be used to occlude autophagy spatiotemporally in living animals.
Potent and specific Atg8-targeting autophagy inhibitory peptides from giant ankyrins.,Li J, Zhu R, Chen K, Zheng H, Zhao H, Yuan C, Zhang H, Wang C, Zhang M Nat Chem Biol. 2018 Jun 4. pii: 10.1038/s41589-018-0082-8. doi:, 10.1038/s41589-018-0082-8. PMID:29867141[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Li J, Zhu R, Chen K, Zheng H, Zhao H, Yuan C, Zhang H, Wang C, Zhang M. Potent and specific Atg8-targeting autophagy inhibitory peptides from giant ankyrins. Nat Chem Biol. 2018 Jun 4. pii: 10.1038/s41589-018-0082-8. doi:, 10.1038/s41589-018-0082-8. PMID:29867141 doi:http://dx.doi.org/10.1038/s41589-018-0082-8
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