TY - JOUR
T1 - Structural assembly of the human Miro1/2 GTPases based on the crystal structure of the N-terminal GTPase domain
AU - Smith, Kyle P.
AU - Focia, Pamela J.
AU - Chakravarthy, Srinivas
AU - Landahl, Eric C.
AU - Klosowiak, Julian L.
AU - Rice, Sarah E
AU - Freymann, Douglas M.
N1 - Publisher Copyright:
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2019/8/8
Y1 - 2019/8/8
N2 - 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 full-length soluble domain of HsMiro1/2.Crystal structure of the human Miro1 N-terminal GTPase bound to GTP, 6D71
AB - 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 full-length soluble domain of HsMiro1/2.Crystal structure of the human Miro1 N-terminal GTPase bound to GTP, 6D71
KW - crystal structure
KW - Gem1p
KW - GTP-binding protein
KW - Miro
KW - mitochondrial dynamics
KW - RhoT
UR - http://www.scopus.com/inward/record.url?scp=85095488858&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85095488858&partnerID=8YFLogxK
U2 - 10.1101/729251
DO - 10.1101/729251
M3 - Article
AN - SCOPUS:85095488858
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
ER -