5ksy › Citations

Structural insights into Parkin substrate lysine targeting from minimal Miro substrates.

Klosowiak JL, Park S, Smith KP, French ME, Focia PJ, Freymann DM, Rice SE
Sci Rep 6 33019 (2016)
Related entries: 5kso, 5ksp, 5ksz, 5kty, 5ku1, 5kut

Cited: 31 times
EuropePMC logo PMID: 27605430

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.

Articles - 5ksy mentioned but not cited (1)

  1. Structural insights into Parkin substrate lysine targeting from minimal Miro substrates. Klosowiak JL, Park S, Smith KP, French ME, Focia PJ, Freymann DM, Rice SE. Sci Rep 6 33019 (2016)


Reviews citing this publication (10)

  1. RBR ligase-mediated ubiquitin transfer: a tale with many twists and turns. Walden H, Rittinger K. Nat Struct Mol Biol 25 440-445 (2018)
  2. Twenty years since the discovery of the parkin gene. Hattori N, Mizuno Y. J Neural Transm (Vienna) 124 1037-1054 (2017)
  3. Multitasking guardian of mitochondrial quality: Parkin function and Parkinson's disease. Kamienieva I, Duszyński J, Szczepanowska J. Transl Neurodegener 10 5 (2021)
  4. Miro: A molecular switch at the center of mitochondrial regulation. Eberhardt EL, Ludlam AV, Tan Z, Cianfrocco MA. Protein Sci 29 1269-1284 (2020)
  5. The Emerging Role of RHOT1/Miro1 in the Pathogenesis of Parkinson's Disease. Grossmann D, Berenguer-Escuder C, Chemla A, Arena G, Krüger R. Front Neurol 11 587 (2020)
  6. Mechanisms of Non-Vesicular Exchange of Lipids at Membrane Contact Sites: Of Shuttles, Tunnels and, Funnels. Egea PF. Front Cell Dev Biol 9 784367 (2021)
  7. Mitophagy and Neurodegeneration: Between the Knowns and the Unknowns. Jetto CT, Nambiar A, Manjithaya R. Front Cell Dev Biol 10 837337 (2022)
  8. Mitochondrial Miro GTPases coordinate mitochondrial and peroxisomal dynamics. Zinsmaier KE. Small GTPases 12 372-398 (2021)
  9. Proteolytic regulation of mitochondrial dynamics. Dietz JV, Bohovych I, Viana MP, Khalimonchuk O. Mitochondrion 49 289-304 (2019)
  10. Transmembrane Membrane Readers form a Novel Class of Proteins That Include Peripheral Phosphoinositide Recognition Domains and Viral Spikes. Overduin M, Tran A, Eekels DM, Overduin F, Kervin TA. Membranes (Basel) 12 1161 (2022)

Articles citing this publication (20)

  1. Parkin targets HIF-1α for ubiquitination and degradation to inhibit breast tumor progression. Liu J, Zhang C, Zhao Y, Yue X, Wu H, Huang S, Chen J, Tomsky K, Xie H, Khella CA, Gatza ML, Xia D, Gao J, White E, Haffty BG, Hu W, Feng Z. Nat Commun 8 1823 (2017)
  2. Miro1-mediated mitochondrial positioning shapes intracellular energy gradients required for cell migration. Schuler MH, Lewandowska A, Caprio GD, Skillern W, Upadhyayula S, Kirchhausen T, Shaw JM, Cunniff B. Mol Biol Cell 28 2159-2169 (2017)
  3. Miro proteins prime mitochondria for Parkin translocation and mitophagy. Safiulina D, Kuum M, Choubey V, Gogichaishvili N, Liiv J, Hickey MA, Cagalinec M, Mandel M, Zeb A, Liiv M, Kaasik A. EMBO J 38 e99384 (2019)
  4. A PGAM5-KEAP1-Nrf2 complex is required for stress-induced mitochondrial retrograde trafficking. O'Mealey GB, Plafker KS, Berry WL, Janknecht R, Chan JY, Plafker SM. J Cell Sci 130 3467-3480 (2017)
  5. Identification of Miro1 and Miro2 as mitochondrial receptors for myosin XIX. Oeding SJ, Majstrowicz K, Hu XP, Schwarz V, Freitag A, Honnert U, Nikolaus P, Bähler M. J Cell Sci 131 jcs219469 (2018)
  6. Miro1 Marks Parkinson's Disease Subset and Miro1 Reducer Rescues Neuron Loss in Parkinson's Models. Hsieh CH, Li L, Vanhauwaert R, Nguyen KT, Davis MD, Bu G, Wszolek ZK, Wang X. Cell Metab 30 1131-1140.e7 (2019)
  7. Impaired mitochondrial-endoplasmic reticulum interaction and mitophagy in Miro1-mutant neurons in Parkinson's disease. Berenguer-Escuder C, Grossmann D, Antony P, Arena G, Wasner K, Massart F, Jarazo J, Walter J, Schwamborn JC, Grünewald A, Krüger R. Hum Mol Genet 29 1353-1364 (2020)
  8. Loss of neuronal Miro1 disrupts mitophagy and induces hyperactivation of the integrated stress response. López-Doménech G, Howden JH, Covill-Cooke C, Morfill C, Patel JV, Bürli R, Crowther D, Birsa N, Brandon NJ, Kittler JT. EMBO J 40 e100715 (2021)
  9. ER-mitochondria contacts promote mitochondrial-derived compartment biogenesis. English AM, Schuler MH, Xiao T, Kornmann B, Shaw JM, Hughes AL. J Cell Biol 219 e202002144 (2020)
  10. Crystal structure and calcium-induced conformational changes of diacylglycerol kinase α EF-hand domains. Takahashi D, Suzuki K, Sakamoto T, Iwamoto T, Murata T, Sakane F. Protein Sci 28 694-706 (2019)
  11. Impact of altered phosphorylation on loss of function of juvenile Parkinsonism-associated genetic variants of the E3 ligase parkin. Aguirre JD, Dunkerley KM, Lam R, Rusal M, Shaw GS. J Biol Chem 293 6337-6348 (2018)
  12. Insight into human Miro1/2 domain organization based on the structure of its N-terminal GTPase. Smith KP, Focia PJ, Chakravarthy S, Landahl EC, Klosowiak JL, Rice SE, Freymann DM. J Struct Biol 212 107656 (2020)
  13. Human Miro Proteins Act as NTP Hydrolases through a Novel, Non-Canonical Catalytic Mechanism. Peters DT, Kay L, Eswaran J, Lakey JH, Soundararajan M. Int J Mol Sci 19 E3839 (2018)
  14. Discovery of small-molecule positive allosteric modulators of Parkin E3 ligase. Shlevkov E, Murugan P, Montagna D, Stefan E, Hadzipasic A, Harvey JS, Kumar PR, Entova S, Bansal N, Bickford S, Wong LY, Hirst WD, Weihofen A, Silvian LF. iScience 25 103650 (2022)
  15. Distinct phosphorylation signals drive acceptor versus free ubiquitin chain targeting by parkin. Dunkerley KM, Rintala-Dempsey AC, Salzano G, Tadayon R, Hadi D, Barber KR, Walden H, Shaw GS. Biochem J 479 751-766 (2022)
  16. Epithelial Ablation of Miro1/Rhot1 GTPase Augments Lung Inflammation by Cigarette Smoke. Sharma S, Wang Q, Muthumalage T, Rahman I. Pathophysiology 28 501-512 (2021)
  17. Miro1 R272Q disrupts mitochondrial calcium handling and neurotransmitter uptake in dopaminergic neurons. Schwarz L, Sharma K, Dodi LD, Rieder LS, Fallier-Becker P, Casadei N, Fitzgerald JC. Front Mol Neurosci 15 966209 (2022)
  18. Solution structure and dynamics of the mitochondrial-targeted GTPase-activating protein (GAP) VopE by an integrated NMR/SAXS approach. Smith KP, Lee W, Tonelli M, Lee Y, Light SH, Cornilescu G, Chakravarthy S. Protein Sci 31 e4282 (2022)
  19. Interaction between the mitochondrial adaptor MIRO and the motor adaptor TRAK. Baltrusaitis EE, Ravitch EE, Fenton AR, Perez TA, Holzbaur ELF, Dominguez R. J Biol Chem 299 105441 (2023)
  20. Monitoring PARKIN RBR Ubiquitin Ligase Activation States with UbFluor. Foote PK, Statsyuk AV. Curr Protoc Chem Biol 10 e45 (2018)


Quick links