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TitleCryo-EM structures of the human Elongator complex at work.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 4094, Year 2024
Publish dateMay 15, 2024
AuthorsNour-El-Hana Abbassi / Marcin Jaciuk / David Scherf / Pauline Böhnert / Alexander Rau / Alexander Hammermeister / Michał Rawski / Paulina Indyka / Grzegorz Wazny / Andrzej Chramiec-Głąbik / Dominika Dobosz / Bozena Skupien-Rabian / Urszula Jankowska / Juri Rappsilber / Raffael Schaffrath / Ting-Yu Lin / Sebastian Glatt /
PubMed AbstracttRNA modifications affect ribosomal elongation speed and co-translational folding dynamics. The Elongator complex is responsible for introducing 5-carboxymethyl at wobble uridine bases (cmU) in ...tRNA modifications affect ribosomal elongation speed and co-translational folding dynamics. The Elongator complex is responsible for introducing 5-carboxymethyl at wobble uridine bases (cmU) in eukaryotic tRNAs. However, the structure and function of human Elongator remain poorly understood. In this study, we present a series of cryo-EM structures of human ELP123 in complex with tRNA and cofactors at four different stages of the reaction. The structures at resolutions of up to 2.9 Å together with complementary functional analyses reveal the molecular mechanism of the modification reaction. Our results show that tRNA binding exposes a universally conserved uridine at position 33 (U), which triggers acetyl-CoA hydrolysis. We identify a series of conserved residues that are crucial for the radical-based acetylation of U and profile the molecular effects of patient-derived mutations. Together, we provide the high-resolution view of human Elongator and reveal its detailed mechanism of action.
External linksNat Commun / PubMed:38750017 / PubMed Central
MethodsEM (single particle)
Resolution2.87 - 4.25 Å
Structure data

EMDB-17924, PDB-8ptx:
Cryo-EM structure of human Elp123 in complex with tRNA, acetyl-CoA, 5'-deoxyadenosine and methionine
Method: EM (single particle) / Resolution: 2.87 Å

EMDB-17925, PDB-8pty:
Cryo-EM structure of human Elp123 in complex with 5'-deoxyadenosine and methionine
Method: EM (single particle) / Resolution: 3.58 Å

EMDB-17926, PDB-8ptz:
Cryo-EM structure of human Elp123 in complex with tRNA, S-ethyl-CoA, 5'-deoxyadenosine and methionine
Method: EM (single particle) / Resolution: 3.35 Å

EMDB-17927, PDB-8pu0:
Cryo-EM structure of human Elp123 in complex with tRNA, desulpho-CoA, 5'-deoxyadenosine and methionine
Method: EM (single particle) / Resolution: 4.25 Å

Chemicals

ChemComp-SF4:
IRON/SULFUR CLUSTER / Iron–sulfur cluster

ChemComp-5AD:
5'-DEOXYADENOSINE / Deoxyadenosine

ChemComp-ACO:
ACETYL COENZYME *A / Acetyl-CoA

ChemComp-MET:
METHIONINE / Methionine

ChemComp-MG:
Unknown entry


ChemComp, No image

ChemComp-A2U:
Unknown entry

ChemComp-DCA:
DESULFO-COENZYME A

Source
  • homo sapiens (human)
KeywordsTRANSLATION / Elongator / tRNA modification / acetyl-CoA hydrolysis

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