5KTY

hMiro EF hand and cGTPase domains, GDP and Ca2+ bound state

5KTY の概要

• エントリーDOI: 10.2210/pdb5kty/pdb
• 関連するPDBエントリー: 5KSO 5KSP 5KSY 5KSZ 5KU1 5KUT
• 分子名称: Mitochondrial Rho GTPase 1, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: miro, gtpase, parkin, mitochondria, hydrolase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Mitochondrion outer membrane ; Single-pass type IV membrane protein : Q8IXI2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 50056.72

構造登録者

Klosowiak, J.L.,Focia, P.J.,Rice, S.E.,Freymann, D.M. (登録日: 2016-07-12, 公開日: 2016-09-21, 最終更新日: 2023-10-04)

主引用文献

Klosowiak, J.L.,Park, S.,Smith, K.P.,French, M.E.,Focia, P.J.,Freymann, D.M.,Rice, S.E.
Structural insights into Parkin substrate lysine targeting from minimal Miro substrates.
Sci Rep, 6:33019-33019, 2016

PubMed Abstract: Hereditary Parkinson's disease is commonly caused by mutations in the protein kinase PINK1 or the E3 ubiquitin ligase Parkin, which function together to eliminate damaged mitochondria. PINK1 phosphorylates both Parkin and ubiquitin to stimulate ubiquitination of dozens of proteins on the surface of the outer mitochondrial membrane. However, the mechanisms by which Parkin recognizes specific proteins for modification remain largely unexplored. Here, we show that the C-terminal GTPase (cGTPase) of the Parkin primary substrate human Miro is necessary and sufficient for efficient ubiquitination. We present several new X-ray crystal structures of both human Miro1 and Miro2 that reveal substrate recognition and ubiquitin transfer to be specific to particular protein domains and lysine residues. We also provide evidence that Parkin substrate recognition is functionally separate from substrate modification. Finally, we show that prioritization for modification of a specific lysine sidechain of the cGTPase (K572) within human Miro1 is dependent on both its location and chemical microenvironment. Activation of Parkin by phosphorylation or by binding of pUb is required for prioritization of K572 for modification, suggesting that Parkin activation and acquisition of substrate specificity are coupled.

PubMed: 27605430
DOI: 10.1038/srep33019

実験手法

X-RAY DIFFRACTION (2.522 Å)