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NAC promotes co-translational protein folding at the ribosomal tunnel exit

ABSTRACT: The nascent polypeptide-associated complex (NAC) is crucial for protein biogenesis, coordinating enzymatic modifications and membrane targeting of nascent chains at the ribosomal tunnel exit. However, its role in co-translational folding remains unclear. Here, we report the genome-wide profiling of NAC interactions with nascent chains in human cells, demonstrating that it correlates with emerging segments of folded domains of cytonuclear proteins. Single-molecule and structural analyses revealed that NAC’s b-barrel domain dynamically interacts with the ribosome and emerging chains at the tunnel exit, presumably facilitating initial compaction and early folding, and that NAC binding promotes native folding of proteins. Additionally, we uncovered compartment-specific nascent chain interactions of NAC, supporting it’s role in targeting proteins to the endoplasmic reticulum and in mitochondrial membrane protein biogenesis. Together, these findings establish NAC as a bona fide co-translational chaperone that facilitates early protein folding at the ribosomal tunnel exit, expanding its functional repertoire in protein biogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE290865 | GEO | 2026/03/23

REPOSITORIES: GEO

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