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| | ==human m-AAA protease AFG3L2, substrate-bound== | | ==human m-AAA protease AFG3L2, substrate-bound== |
| - | <StructureSection load='6nyy' size='340' side='right'caption='[[6nyy]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <SX load='6nyy' size='340' side='right' viewer='molstar' caption='[[6nyy]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6nyy]] is a 10 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=6NYY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NYY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6nyy]] is a 10 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=6NYY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NYY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <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">Electron Microscopy, [[Resolution|Resolution]] 3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AFG3L2 ([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=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC+ACID-ADENYLATE+ESTER'>ANP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <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=6nyy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nyy OCA], [http://pdbe.org/6nyy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nyy RCSB], [http://www.ebi.ac.uk/pdbsum/6nyy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nyy 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=6nyy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nyy OCA], [https://pdbe.org/6nyy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6nyy RCSB], [https://www.ebi.ac.uk/pdbsum/6nyy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6nyy ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/AFG32_HUMAN AFG32_HUMAN]] Spinocerebellar ataxia type 28;Early-onset spastic ataxia-neuropathy syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/AFG32_HUMAN AFG32_HUMAN] Spinocerebellar ataxia type 28;Early-onset spastic ataxia-neuropathy syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AFG32_HUMAN AFG32_HUMAN]] ATP-dependent protease which is essential for axonal development (By similarity). | + | [https://www.uniprot.org/uniprot/AFG32_HUMAN AFG32_HUMAN] ATP-dependent protease which is essential for axonal development (By similarity). |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Mitochondrial AAA+ quality-control proteases regulate diverse aspects of mitochondrial biology through specialized protein degradation, but the underlying mechanisms of these enzymes remain poorly defined. The mitochondrial AAA+ protease AFG3L2 is of particular interest, as genetic mutations localized throughout AFG3L2 are linked to diverse neurodegenerative disorders. However, a lack of structural data has limited our understanding of how mutations impact enzymatic function. Here, we used cryoelectron microscopy (cryo-EM) to determine a substrate-bound structure of the catalytic core of human AFG3L2. This structure identifies multiple specialized structural features that integrate with conserved motifs required for ATP-dependent translocation to unfold and degrade targeted proteins. Many disease-relevant mutations localize to these unique structural features of AFG3L2 and distinctly influence its activity and stability. Our results provide a molecular basis for neurological phenotypes associated with different AFG3L2 mutations and establish a structural framework to understand how different members of the AAA+ superfamily achieve specialized biological functions.
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| - | | + | |
| - | Unique Structural Features of the Mitochondrial AAA+ Protease AFG3L2 Reveal the Molecular Basis for Activity in Health and Disease.,Puchades C, Ding B, Song A, Wiseman RL, Lander GC, Glynn SE Mol Cell. 2019 Jul 11. pii: S1097-2765(19)30472-1. doi:, 10.1016/j.molcel.2019.06.016. PMID:31327635<ref>PMID:31327635</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 6nyy" style="background-color:#fffaf0;"></div>
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| - | == References ==
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| - | <references/>
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| | __TOC__ | | __TOC__ |
| - | </StructureSection> | + | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lander, G C]] | + | [[Category: Lander GC]] |
| - | [[Category: Puchades, C]] | + | [[Category: Puchades C]] |
| - | [[Category: Aaa+]]
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| - | [[Category: Afg3l2]]
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| - | [[Category: Atpase]]
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| - | [[Category: Inner membrane]]
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| - | [[Category: M/aaa protease]]
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| - | [[Category: Mitochondria]]
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| - | [[Category: Neurodegeneration]]
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| - | [[Category: Protease]]
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| - | [[Category: Protein quality control]]
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| - | [[Category: Translocase]]
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