Insight into human Miro1/2 domain organization based on the structure of its N-terminal GTPase.

ABSTRACT: 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.

SUBMITTER: Smith KP 

PROVIDER: S-EPMC7744357 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature