# NatA engages in multi-factor complexes at the ribosomal polypeptide tunnel exit

## TL;DR

This paper shows that the NatA enzyme forms multi-protein complexes at the ribosome, helping to coordinate protein modifications during their creation.

## Contribution

The study reveals that NatA acts as an interaction hub, forming diverse multi-factor complexes at the ribosomal tunnel exit.

## Key findings

- NatA can form ribosome-independent assemblies with ribosome-associated factors (RAFs).
- NatA forms a ternary complex with Ebp1 or a second copy of NatA at the ribosome.
- A conserved binding site on NatA allows interactions with four RAFs, enabling diverse complex formation.

## Abstract

N-terminal acetylation (NTA) is the most common protein modification in eukaryotes, playing a crucial role in proteostasis. Almost 40% of the human proteome is acetylated co-translationally by the NatA complex, which requires prior N-terminal methionine excision (NME). Recently, NatA was shown to form multi-enzyme complexes with MAP1/NAC or MAP2, combining the capabilities of NME and NTA into a single complex. Here, we show that NatA can also form ribosome-independent assemblies with several ribosome associated factors (RAFs). At the ribosome, NatA can form a ternary complex with the abundant pseudoenzyme Ebp1 or a second copy of NatA, which can be coordinated from a different binding site with closer access to a potential substrate. Further, we identify a conserved binding site on NatA, which can be accessed by four RAFs - Ebp1, NAC, Naa10 and HypK, allowing the formation of different multi-factor complexes at the ribosomal tunnel exit. Therefore, our data suggest that NatA constitutes an interaction hub, and contributes to the coordination of co-translational protein maturation.

N-terminal acetylation shapes protein fate during protein biosynthesis at the ribosome. Here the authors show that the NatA enzyme forms dynamic multi-factor complexes at the ribosome, acting as an interaction hub that coordinates cotranslational protein maturation.