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; Rice, Sarah E.

doi:10.1038/embor.2013.151

Cited by 73 publications

(104 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More surprising is the fact that Drosophila Miro shows minimal structural changes, whether the protein is Ca 2 + bound or Ca 2 + free [29]. This is in stark contrast with other EF-hand proteins, and difficult to reconcile with the strong effects of Ca 2 + on mitochondrial transport.…”

Section: The Miro Gtpases Mechanism and Functionmentioning

confidence: 83%

“…The cytosolic domain of Miro consists of two GTPase domains flanking two calcium-binding EFhands (Figure 2A). An X-ray structure of a Drosophila Miro containing both EF-hands and the C-terminal GTPase (cGTPase) domain shows high structure similarity to the cGTPase domain of the Rheb GTPase, a subfamily of RAS [29].…”

Section: The Miro Gtpases Mechanism and Functionmentioning

confidence: 99%

See 1 more Smart Citation

Dynamics of the mitochondrial network during mitosis

Kanfer

Kornmann

2016

Biochemical Society Transactions

View full text Add to dashboard Cite

During mitosis, cells undergo massive deformation and reorganization, impacting on all cellular structures. Mitochondria, in particular, are highly dynamic organelles, which constantly undergo events of fission, fusion and cytoskeleton-based transport. This plasticity ensures the proper distribution of the metabolism, and the proper inheritance of functional organelles. During cell cycle, mitochondria undergo dramatic changes in distribution. In this review, we focus on the dynamic events that target mitochondria during mitosis. We describe how the cell-cycle-dependent microtubule-associated protein centromeric protein F (Cenp-F) is recruited to mitochondria by the mitochondrial Rho GTPase (Miro) to promote mitochondrial transport and re-distribution following cell division.

show abstract

Section: The Miro Gtpases Mechanism and Functionmentioning

confidence: 83%

Section: The Miro Gtpases Mechanism and Functionmentioning

confidence: 99%

Dynamics of the mitochondrial network during mitosis

Kanfer

Kornmann

2016

Biochemical Society Transactions

View full text Add to dashboard Cite

show abstract

“…The connecting short α-helix of CD EFhd2 resembles the ligand helix of EF-hand proteins. Thus, we named this helix the LM-helix27. In addition, two Ca 2+ ions are coordinated by several negative charged residues (Asp105, Asp109 and Glu116 for EF1; Asp141, Asp143, Asp145 and Glu152 for EF2), which are well-known Ca 2+ -coordinating residues in EF-hand domains (Fig.…”

Section: Resultsmentioning

confidence: 99%

Structural implications of Ca2+-dependent actin-bundling function of human EFhd2/Swiprosin-1

Park

Kwon

et al. 2016

Sci Rep

View full text Add to dashboard Cite

EFhd2/Swiprosin-1 is a cytoskeletal Ca2+-binding protein implicated in Ca2+-dependent cell spreading and migration in epithelial cells. EFhd2 domain architecture includes an N-terminal disordered region, a PxxP motif, two EF-hands, a ligand mimic helix and a C-terminal coiled-coil domain. We reported previously that EFhd2 displays F-actin bundling activity in the presence of Ca2+ and this activity depends on the coiled-coil domain and direct interaction of the EFhd2 core region. However, the molecular mechanism for the regulation of F-actin binding and bundling by EFhd2 is unknown. Here, the Ca2+-bound crystal structure of the EFhd2 core region is presented and structures of mutants defective for Ca2+-binding are also described. These structures and biochemical analyses reveal that the F-actin bundling activity of EFhd2 depends on the structural rigidity of F-actin binding sites conferred by binding of the EF-hands to Ca2+. In the absence of Ca2+, the EFhd2 core region exhibits local conformational flexibility around the EF-hand domain and C-terminal linker, which retains F-actin binding activity but loses the ability to bundle F-actin. In addition, we establish that dimerisation of EFhd2 via the C-terminal coiled-coil domain, which is necessary for F-actin bundling, occurs through the parallel coiled-coil interaction.

show abstract

“…MIRO proteins were initially identified on the outer mitochondrial membrane21 where they, together with TRAK1/2, link the microtubule motors kinesin and dynein to mitochondria,22, 23, 24, 25 and play key roles in mitochondrial motility, homeostasis and inheritance 26, 27. Mammalian MIRO1 and MIRO2 share 60% similarity and an analogous structure containing 2 GTPase and 2 EF‐hand calcium binding domains 21, 28. Studies on mammalian MIRO proteins have focused mainly on MIRO1 due to its clear role in mitochondrial motility, particularly in neurons 22, 25.…”

Section: Introductionmentioning

confidence: 99%

A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics of peroxisomes

Castro

Richards

Metz

et al. 2018

Traffic

123

View full text Add to dashboard Cite

Peroxisomes are dynamic organelles which fulfil essential roles in lipid and ROS metabolism. Peroxisome movement and positioning allows interaction with other organelles and is crucial for their cellular function. In mammalian cells, such movement is microtubule‐dependent and mediated by kinesin and dynein motors. The mechanisms of motor recruitment to peroxisomes are largely unknown, as well as the role this plays in peroxisome membrane dynamics and proliferation. Here, using a combination of microscopy, live‐cell imaging analysis and mathematical modelling, we identify a role for Mitochondrial Rho GTPase 1 (MIRO1) as an adaptor for microtubule‐dependent peroxisome motility in mammalian cells. We show that MIRO1 is targeted to peroxisomes and alters their distribution and motility. Using a peroxisome‐targeted MIRO1 fusion protein, we demonstrate that MIRO1‐mediated pulling forces contribute to peroxisome membrane elongation and proliferation in cellular models of peroxisome disease. Our findings reveal a molecular mechanism for establishing peroxisome‐motor protein associations in mammalian cells and provide new insights into peroxisome membrane dynamics in health and disease.

show abstract

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

Cited by 73 publications

References 31 publications

Dynamics of the mitochondrial network during mitosis

Dynamics of the mitochondrial network during mitosis

Structural implications of Ca2+-dependent actin-bundling function of human EFhd2/Swiprosin-1

A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics of peroxisomes

Contact Info

Product

Resources

About