3-Dimensional architecture of the human multi-tRNA synthetase complex.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
04 09 2020
04 09 2020
Historique:
accepted:
06
07
2020
revised:
08
06
2020
received:
13
03
2020
pubmed:
10
7
2020
medline:
21
10
2020
entrez:
10
7
2020
Statut:
ppublish
Résumé
In mammalian cells, eight cytoplasmic aminoacyl-tRNA synthetases (AARS), and three non-synthetase proteins, reside in a large multi-tRNA synthetase complex (MSC). AARSs have critical roles in interpretation of the genetic code during protein synthesis, and in non-canonical functions unrelated to translation. Nonetheless, the structure and function of the MSC remain unclear. Partial or complete crystal structures of all MSC constituents have been reported; however, the structure of the holo-MSC has not been resolved. We have taken advantage of cross-linking mass spectrometry (XL-MS) and molecular docking to interrogate the three-dimensional architecture of the MSC in human HEK293T cells. The XL-MS approach uniquely provides structural information on flexibly appended domains, characteristic of nearly all MSC constituents. Using the MS-cleavable cross-linker, disuccinimidyl sulfoxide, inter-protein cross-links spanning all MSC constituents were observed, including cross-links between eight protein pairs not previously known to interact. Intra-protein cross-links defined new structural relationships between domains in several constituents. Unexpectedly, an asymmetric AARS distribution was observed featuring a clustering of tRNA anti-codon binding domains on one MSC face. Possibly, the non-uniform localization improves efficiency of delivery of charged tRNA's to an interacting ribosome during translation. In summary, we show a highly compact, 3D structural model of the human holo-MSC.
Identifiants
pubmed: 32644155
pii: 5869352
doi: 10.1093/nar/gkaa569
pmc: PMC7470956
doi:
Substances chimiques
Multiprotein Complexes
0
Amino Acyl-tRNA Synthetases
EC 6.1.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8740-8754Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL128300
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128268
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM086430
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL029582
Pays : United States
Organisme : NIH HHS
ID : S10 OD023436
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK123236
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK124203
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL076491
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.
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