Insight into human Miro1/2 domain organization based on the structure of its N-terminal GTPase
| Autor: | Kyle P. Smith, Eric C. Landahl, Douglas M. Freymann, Pamela J. Focia, Sarah E. Rice, Julian L. Klosowiak, Srinivas Chakravarthy |
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| Rok vydání: | 2020 |
| Předmět: |
rho GTP-Binding Proteins
GTP' G protein Protein Data Bank (RCSB PDB) GTPase Article Outer mitochondrial membrane GTP Phosphohydrolases Mitochondrial Proteins 03 medical and health sciences Protein Domains X-Ray Diffraction Structural Biology Scattering Small Angle Humans Amino Acid Sequence 030304 developmental biology 0303 health sciences biology Chemistry 030302 biochemistry & molecular biology Active site Signal transducing adaptor protein Mitochondria Cell biology Mitochondrial Membranes Domain (ring theory) biology.protein |
| Zdroj: | J Struct Biol |
| ISSN: | 1047-8477 |
| Popis: | Dysfunction in mitochondrial dynamics is believed to contribute to a host of neurological disorders and has recently been implicated in cancer metastasis. The outer mitochondrial membrane adapter protein Miro functions in the regulation of mitochondrial mobility and degradation, however, the structural basis for its roles in mitochondrial regulation remain unknown. Here, we report a 1.7Å crystal structure of N-terminal GTPase domain (nGTPase) of human Miro1 bound unexpectedly to GTP, thereby revealing a non-catalytic configuration of the putative GTPase active site. We identify two conserved surfaces of the nGTPase, the "SELFYY" and "ITIP" motifs, that are potentially positioned to mediate dimerization or interaction with binding partners. Additionally, we report small angle X-ray scattering (SAXS) data obtained from the intact soluble HsMiro1 and its paralog HsMiro2. Taken together, the data allow modeling of a crescent-shaped assembly of the soluble domain of HsMiro1/2. PDB RSEFERENCE: Crystal structure of the human Miro1 N-terminal GTPase bound to GTP, 6D71. |
| Databáze: | OpenAIRE |
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