5KSP

hMiro1 C-domain GDP Complex C2221 Crystal Form

Summary for 5KSP

• Entry DOI: 10.2210/pdb5ksp/pdb
• Related: 5KSO 5KSY 5KSZ 5KTY 5KU1 5KUT
• Descriptor: Mitochondrial Rho GTPase 1, GUANOSINE-5'-DIPHOSPHATE, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: miro, gtpase, parkin, mitochondria, hydrolase
• Biological source: Homo sapiens (Human)
• Cellular location: Mitochondrion outer membrane ; Single-pass type IV membrane protein : Q8IXI2
• Total number of polymer chains: 2
• Total formula weight: 44960.14

Authors

Klosowiak, J.L.,Focia, P.J.,Rice, S.E.,Freymann, D.M. (deposition date: 2016-07-08, release date: 2016-09-21, Last modification date: 2023-10-04)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.162 Å)