9FQ0

Human NatA-NAC-MAP1 80S ribosome complex

This is a non-PDB format compatible entry.

Summary for 9FQ0

• Entry DOI: 10.2210/pdb9fq0/pdb
• EMDB information: 50642
• Descriptor: 5.8S rRNA, 60S ribosomal protein L19, 60S ribosomal protein L38, ... (17 entities in total)
• Functional Keywords: co-translational processing, ribosome associated factor (raf), methionine aminopeptidase 2 (map2), n-terminal methionine excision (nme), n-acetyl-transferase a (nata), n-termional acetylation (nta), uba domain, a-solenoid, protein-protein and protein-rna interactions, translation
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 16
• Total formula weight: 2060568.41

Authors

Klein, M.A.,Wild, K.,Sinning, I. (deposition date: 2024-06-14, release date: 2024-07-03, Last modification date: 2024-10-02)

Primary citation

Klein, M.,Wild, K.,Sinning, I.
Multi-protein assemblies orchestrate co-translational enzymatic processing on the human ribosome.
Nat Commun, 15:7681-7681, 2024

PubMed Abstract: Nascent chains undergo co-translational enzymatic processing as soon as their N-terminus becomes accessible at the ribosomal polypeptide tunnel exit (PTE). In eukaryotes, N-terminal methionine excision (NME) by Methionine Aminopeptidases (MAP1 and MAP2), and N-terminal acetylation (NTA) by N-Acetyl-Transferase A (NatA), is the most common combination of subsequent modifications carried out on the 80S ribosome. How these enzymatic processes are coordinated in the context of a rapidly translating ribosome has remained elusive. Here, we report two cryo-EM structures of multi-enzyme complexes assembled on vacant human 80S ribosomes, indicating two routes for NME-NTA. Both assemblies form on the 80S independent of nascent chain substrates. Irrespective of the route, NatA occupies a non-intrusive 'distal' binding site on the ribosome which does not interfere with MAP1 or MAP2 binding nor with most other ribosome-associated factors (RAFs). NatA can partake in a coordinated, dynamic assembly with MAP1 through the hydra-like chaperoning function of the abundant Nascent Polypeptide-Associated Complex (NAC). In contrast to MAP1, MAP2 completely covers the PTE and is thus incompatible with NAC and MAP1 recruitment. Together, our data provide the structural framework for the coordinated orchestration of NME and NTA in protein biogenesis.

PubMed: 39227397
DOI: 10.1038/s41467-024-51964-9

Experimental method

ELECTRON MICROSCOPY (4.67 Å)