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

The nascent polypeptide-associated complex (NAC) coordinates enzymatic modifications and membrane targeting of nascent chains during translation. While the role of NAC as a dynamic hub for other factors is well established, its direct role in co-translational folding is unclear. By proteome-wide pro...

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Main Authors: Santos, Jaime (Author) , Günnigmann, Manuel (Author) , Gora, Radoslaw J. (Author) , Iljina, Marija (Author) , Predin, Masa (Author) , Kotan, Ilgin (Author) , De, Pratiman (Author) , Choudhary, Dhawal (Author) , Jang, Juwon (Author) , Tippmann, Frank (Author) , Hins, Christopher (Author) , Ban, Nenad (Author) , Tans, Sander J. (Author) , Shan, Shu-ou (Author) , Kramer, Günter (Author) , Bukau, Bernd (Author)
Format: Article (Journal)
Language:English
Published: 02. April 2026
In: Molecular cell
Year: 2026, Volume: 86, Issue: 7, Pages: 1311-1326,e1-e11
ISSN:1097-4164
DOI:10.1016/j.molcel.2026.02.022
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.molcel.2026.02.022
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S109727652600136X
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Author Notes:Jaime Santos, Manuel Günnigmann, Radoslaw J. Gora, Marija Iljina, Masa Predin, Ilgin Eser Kotan, Pratiman De, Dhawal Choudhary, Juwon Jang, Frank Tippmann, Christopher Hins, Nenad Ban, Sander J. Tans, Shu-ou Shan, Günter Kramer, Bernd Bukau
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Summary:The nascent polypeptide-associated complex (NAC) coordinates enzymatic modifications and membrane targeting of nascent chains during translation. While the role of NAC as a dynamic hub for other factors is well established, its direct role in co-translational folding is unclear. By proteome-wide profiling of co-translational NAC interactions in human cells, we found that NAC recognizes emerging segments enriched in hydrophobicity and α-helical propensity within folded domains of cytonuclear proteins. Single-molecule and structural analyses reveal that NAC, via its β-barrel domain, dynamically interacts with nascent chains at the ribosomal tunnel exit and is capable of promoting on-pathway folding. Compartment-specific nascent chain interactions of NAC further elucidate its role in targeting to the endoplasmic reticulum and in mitochondrial membrane protein biogenesis. Together, these findings show that human NAC acts as a bona fide co-translational chaperone that directly promotes early protein folding at the ribosomal tunnel exit, expanding its functional repertoire in protein biogenesis.
Item Description:Gesehen am 18.05.2026
Online verfügbar: 23. März 2026, Artikel-Version: 2. April 2026
Physical Description:Online Resource
ISSN:1097-4164
DOI:10.1016/j.molcel.2026.02.022

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