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-Structure paper
タイトル | Unique Structural Features of the Mitochondrial AAA+ Protease AFG3L2 Reveal the Molecular Basis for Activity in Health and Disease. |
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ジャーナル・号・ページ | Mol Cell, Vol. 75, Issue 5, Page 1073-11085.e6, Year 2019 |
掲載日 | 2019年9月5日 |
![]() | Cristina Puchades / Bojian Ding / Albert Song / R Luke Wiseman / Gabriel C Lander / Steven E Glynn / ![]() |
PubMed 要旨 | Mitochondrial AAA+ quality-control proteases regulate diverse aspects of mitochondrial biology through specialized protein degradation, but the underlying mechanisms of these enzymes remain poorly ...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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手法 | EM (単粒子) |
解像度 | 3.0 Å |
構造データ | |
化合物 | ![]() ChemComp-ZN: ![]() ChemComp-ANP: ![]() ChemComp-MG: ![]() ChemComp-ADP: |
由来 |
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![]() | TRANSLOCASE / AAA+ / ATPase / protease / mitochondria / protein quality control / neurodegeneration / inner membrane / AFG3L2 / m/AAA protease |