[English] 日本語
Yorodumi- PDB-7t4m: Structure of dodecameric unphosphorylated Pediculus humanus (Ph) ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7t4m | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Structure of dodecameric unphosphorylated Pediculus humanus (Ph) PINK1 D357A mutant | |||||||||
Components | Serine/threonine-protein kinase PINK1, putative | |||||||||
Keywords | TRANSFERASE / PINK1 / Kinase / Mitophagy / Parkinson's Disease / Ubiquitin / Phosphorylation / Phospho-ubiquitin | |||||||||
Function / homology | Function and homology information positive regulation of mitochondrial fission / autophagy / regulation of apoptotic process / mitochondrial outer membrane / non-specific serine/threonine protein kinase / mitochondrial inner membrane / protein kinase activity / protein serine/threonine kinase activity / ATP binding / metal ion binding / cytosol Similarity search - Function | |||||||||
Biological species | Pediculus humanus corporis (human body louse) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.48 Å | |||||||||
Authors | Gan, Z.Y. / Leis, A. / Dewson, G. / Glukhova, A. / Komander, D. | |||||||||
Funding support | United States, 2items
| |||||||||
Citation | Journal: Nature / Year: 2022 Title: Activation mechanism of PINK1. Authors: Zhong Yan Gan / Sylvie Callegari / Simon A Cobbold / Thomas R Cotton / Michael J Mlodzianoski / Alexander F Schubert / Niall D Geoghegan / Kelly L Rogers / Andrew Leis / Grant Dewson / Alisa ...Authors: Zhong Yan Gan / Sylvie Callegari / Simon A Cobbold / Thomas R Cotton / Michael J Mlodzianoski / Alexander F Schubert / Niall D Geoghegan / Kelly L Rogers / Andrew Leis / Grant Dewson / Alisa Glukhova / David Komander / Abstract: Mutations in the protein kinase PINK1 lead to defects in mitophagy and cause autosomal recessive early onset Parkinson's disease. PINK1 has many unique features that enable it to phosphorylate ...Mutations in the protein kinase PINK1 lead to defects in mitophagy and cause autosomal recessive early onset Parkinson's disease. PINK1 has many unique features that enable it to phosphorylate ubiquitin and the ubiquitin-like domain of Parkin. Structural analysis of PINK1 from diverse insect species with and without ubiquitin provided snapshots of distinct structural states yet did not explain how PINK1 is activated. Here we elucidate the activation mechanism of PINK1 using crystallography and cryo-electron microscopy (cryo-EM). A crystal structure of unphosphorylated Pediculus humanus corporis (Ph; human body louse) PINK1 resolves an N-terminal helix, revealing the orientation of unphosphorylated yet active PINK1 on the mitochondria. We further provide a cryo-EM structure of a symmetric PhPINK1 dimer trapped during the process of trans-autophosphorylation, as well as a cryo-EM structure of phosphorylated PhPINK1 undergoing a conformational change to an active ubiquitin kinase state. Structures and phosphorylation studies further identify a role for regulatory PINK1 oxidation. Together, our research delineates the complete activation mechanism of PINK1, illuminates how PINK1 interacts with the mitochondrial outer membrane and reveals how PINK1 activity may be modulated by mitochondrial reactive oxygen species. | |||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7t4m.cif.gz | 846.2 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7t4m.ent.gz | 695.6 KB | Display | PDB format |
PDBx/mmJSON format | 7t4m.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7t4m_validation.pdf.gz | 1.4 MB | Display | wwPDB validaton report |
---|---|---|---|---|
Full document | 7t4m_full_validation.pdf.gz | 1.5 MB | Display | |
Data in XML | 7t4m_validation.xml.gz | 126.9 KB | Display | |
Data in CIF | 7t4m_validation.cif.gz | 191.6 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/t4/7t4m ftp://data.pdbj.org/pub/pdb/validation_reports/t4/7t4m | HTTPS FTP |
-Related structure data
Related structure data | 25680MC 7t3xC 7t4kC 7t4lC 7t4nC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
| |||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 |
| |||||||||||||||||||||||||||
Noncrystallographic symmetry (NCS) | NCS domain:
|