EMD-50129

Single-particle
5.75 Å
EMD-50129 Deposition: 18/04/2024
Map released: 04/09/2024
Last modified: 02/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-50129

Mammalian quaternary complex of a translating 80S ribosome, NAC, MetAP1 and NatA/E-HYPK - local refinement

EMD-50129

Single-particle
5.75 Å
EMD-50129 Deposition: 18/04/2024
Map released: 04/09/2024
Last modified: 02/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Oryctolagus cuniculus
Sample: Quaternary complex of a translating 80S ribosome, NAC, MetAP1 and NatA/E-HYPK

Deposition Authors: Yudin D , Scaiola A , Ban N
NAC guides a ribosomal multienzyme complex for nascent protein processing.
Lentzsch AM , Yudin D , Gamerdinger M , Chandrasekar S, Rabl L , Scaiola A , Deuerling E , Ban N , Shan SO
(2024) Nature , 633 , 718 - 724
PUBMED: 39169182
DOI: doi:10.1038/s41586-024-07846-7
ISSN: 1476-4687
ASTM: NATUAS
Abstract:
Approximately 40% of the mammalian proteome undergoes N-terminal methionine excision and acetylation, mediated sequentially by methionine aminopeptidase (MetAP) and N-acetyltransferase A (NatA), respectively1. Both modifications are strictly cotranslational and essential in higher eukaryotic organisms1. The interaction, activity and regulation of these enzymes on translating ribosomes are poorly understood. Here we perform biochemical, structural and in vivo studies to demonstrate that the nascent polypeptide-associated complex2,3 (NAC) orchestrates the action of these enzymes. NAC assembles a multienzyme complex with MetAP1 and NatA early during translation and pre-positions the active sites of both enzymes for timely sequential processing of the nascent protein. NAC further releases the inhibitory interactions from the NatA regulatory protein huntingtin yeast two-hybrid protein K4,5 (HYPK) to activate NatA on the ribosome, enforcing cotranslational N-terminal acetylation. Our results provide a mechanistic model for the cotranslational processing of proteins in eukaryotic cells.