|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal Structure of AnkB LIR/LC3B complex== | | ==Crystal Structure of AnkB LIR/LC3B complex== |
| - | <StructureSection load='5yis' size='340' side='right' caption='[[5yis]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='5yis' size='340' side='right'caption='[[5yis]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5yis]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] 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=5YIS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YIS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5yis]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YIS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YIS 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=PO4:PHOSPHATE+ION'>PO4</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]] 2.201Å</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]), ANK2 ([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=PO4:PHOSPHATE+ION'>PO4</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=5yis FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yis OCA], [http://pdbe.org/5yis PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5yis RCSB], [http://www.ebi.ac.uk/pdbsum/5yis PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5yis 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=5yis FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yis OCA], [https://pdbe.org/5yis PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yis RCSB], [https://www.ebi.ac.uk/pdbsum/5yis PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yis ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[http://www.uniprot.org/uniprot/ANK2_HUMAN ANK2_HUMAN]] Romano-Ward syndrome. Long QT syndrome 4 (LQT4) [MIM:[http://omim.org/entry/600919 600919]]: A heart disorder characterized by a prolonged QT interval on the ECG and polymorphic ventricular arrhythmias. They cause syncope and sudden death in response to exercise or emotional stress, and can present with a sentinel event of sudden cardiac death in infancy. Long QT syndrome type 4 shows many atypical features compared to classical long QT syndromes, including pronounced sinus bradycardia, polyphasic T waves and atrial fibrillation. Cardiac repolarization defects may be not as severe as in classical LQT syndromes and prolonged QT interval on EKG is not a consistent feature. Note=The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:12571597</ref> <ref>PMID:15178757</ref> | |
| | == 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/ANK2_HUMAN ANK2_HUMAN]] In skeletal muscle, required for proper localization of DMD and DCTN4 and for the formation and/or stability of a special subset of microtubules associated with costameres and neuromuscular junctions (By similarity). Attaches integral membrane proteins to cytoskeletal elements. Also binds to cytoskeletal proteins. Required for coordinate assembly of Na/Ca exchanger, Na/K ATPase and InsP3 receptor at sarcoplasmic reticulum sites in cardiomyocytes. Required for the coordinated expression of the Na/K ATPase, Na/Ca exchanger and beta-2-spectrin (SPTBN1) in the inner segment of rod photoreceptors. Required for expression and targeting of SPTBN1 in neonatal cardiomyocytes and for the regulation of neonatal cardiomyocyte contraction rate.<ref>PMID:12571597</ref> | + | [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 == |
| Line 21: |
Line 19: |
| | </div> | | </div> |
| | <div class="pdbe-citations 5yis" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5yis" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Microtubule-associated protein 3D structures|Microtubule-associated protein 3D structures]] |
| | + | *[[Squalene synthase|Squalene synthase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Chen, K]] | + | [[Category: Mus musculus]] |
| - | [[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
|
