28LN

XBP1u-stalled RPL4 RNC in complex with NAC

This is a non-PDB format compatible entry.

Summary for 28LN

• Entry DOI: 10.2210/pdb28ln/pdb
• EMDB information: 56582 56583 56598
• Descriptor: Large ribosomal subunit protein uL4,X-box-binding protein 1, luminal form,X-box-binding protein 1, luminal form,X-box-binding protein 1, luminal form, 60S ribosomal protein L5, Large ribosomal subunit protein eL6, ... (88 entities in total)
• Functional Keywords: nac, chaperone, cotranslational folding, rnc, human 80s, translation
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 86
• Total formula weight: 3945084.61

Authors

Santos, J.,Guennigmann, M.,Gora, R.J.,Iljina, M.,Predin, M.,Kotan, I.E.,De, P.,Choudhary, D.,Jang, J.,Tippmann, F.,Hins, C.,Ban, N.,Tans, S.J.,Shan, S.,Kramer, G.,Bukau, B. (deposition date: 2026-02-05, release date: 2026-06-10)

Primary citation

Santos, J.,Gunnigmann, M.,Gora, R.J.,Iljina, M.,Predin, M.,Kotan, I.E.,De, P.,Choudhary, D.,Jang, J.,Tippmann, F.,Hins, C.,Ban, N.,Tans, S.J.,Shan, S.O.,Kramer, G.,Bukau, B.
NAC promotes co-translational protein folding at the ribosomal tunnel exit.
Mol.Cell, 86:1311-1326.e11, 2026

PubMed Abstract: 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.

PubMed: 41875886
DOI: 10.1016/j.molcel.2026.02.022

Experimental method

ELECTRON MICROSCOPY (2.7 Å)