Structural coupling of the EF hand and C-terminal GTPase domains in the mitochondrial protein Miro

Julian L. Klosowiak, Pamela J Focia, Srinivas Chakravarthy, Eric C. Landahl, Douglas M Freymann, Sarah E Rice*

*Corresponding author for this work

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Miro is a highly conserved calcium-binding GTPase at the regulatory nexus of mitochondrial transport and autophagy. Here we present crystal structures comprising the tandem EF hand and carboxy terminal GTPase (cGTPase) domains of Drosophila Miro. The structures reveal two previously unidentified 'hidden' EF hands, each paired with a canonical EF hand. Each EF hand pair is bound to a helix that structurally mimics an EF hand ligand. A key nucleotide-sensing element and a Pink1 phosphorylation site both lie within an extensive EF hand-cGTPase interface. Our results indicate structural mechanisms for calcium, nucleotide and phosphorylation-dependent regulation of mitochondrial function by Miro.

Original languageEnglish (US)
Pages (from-to)968-974
Number of pages7
JournalEMBO Reports
Volume14
Issue number11
DOIs
StatePublished - Nov 1 2013

Fingerprint

EF Hand Motifs
GTP Phosphohydrolases
Mitochondrial Proteins
Phosphorylation
Nucleotides
Calcium
Crystal structure
Ligands
Autophagy
Drosophila

Keywords

  • EF hand
  • ELM domain
  • GTPase
  • Miro
  • mitochondria

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Biochemistry

Cite this

Klosowiak, Julian L. ; Focia, Pamela J ; Chakravarthy, Srinivas ; Landahl, Eric C. ; Freymann, Douglas M ; Rice, Sarah E. / Structural coupling of the EF hand and C-terminal GTPase domains in the mitochondrial protein Miro. In: EMBO Reports. 2013 ; Vol. 14, No. 11. pp. 968-974.
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Structural coupling of the EF hand and C-terminal GTPase domains in the mitochondrial protein Miro. / Klosowiak, Julian L.; Focia, Pamela J; Chakravarthy, Srinivas; Landahl, Eric C.; Freymann, Douglas M; Rice, Sarah E.

In: EMBO Reports, Vol. 14, No. 11, 01.11.2013, p. 968-974.

Research output: Contribution to journalArticle

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AU - Klosowiak, Julian L.

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AB - Miro is a highly conserved calcium-binding GTPase at the regulatory nexus of mitochondrial transport and autophagy. Here we present crystal structures comprising the tandem EF hand and carboxy terminal GTPase (cGTPase) domains of Drosophila Miro. The structures reveal two previously unidentified 'hidden' EF hands, each paired with a canonical EF hand. Each EF hand pair is bound to a helix that structurally mimics an EF hand ligand. A key nucleotide-sensing element and a Pink1 phosphorylation site both lie within an extensive EF hand-cGTPase interface. Our results indicate structural mechanisms for calcium, nucleotide and phosphorylation-dependent regulation of mitochondrial function by Miro.

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