6NYY

human m-AAA protease AFG3L2, substrate-bound

Summary for 6NYY

• Entry DOI: 10.2210/pdb6nyy/pdb
• EMDB information: 0552
• Descriptor: AFG3-like protein 2, Substrate, ZINC ION, ... (6 entities in total)
• Functional Keywords: aaa+, atpase, protease, mitochondria, protein quality control, neurodegeneration, inner membrane, afg3l2, m/aaa protease, translocase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 355600.42

Authors

Lander, G.C.,Puchades, C. (deposition date: 2019-02-12, release date: 2019-05-22, Last modification date: 2024-03-20)

Primary citation

Puchades, C.,Ding, B.,Song, A.,Wiseman, R.L.,Lander, G.C.,Glynn, S.E.
Unique Structural Features of the Mitochondrial AAA+ Protease AFG3L2 Reveal the Molecular Basis for Activity in Health and Disease.
Mol.Cell, 75:1073-, 2019

PubMed Abstract: 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.

PubMed: 31327635
DOI: 10.1016/j.molcel.2019.06.016

Experimental method

ELECTRON MICROSCOPY (3 Å)