epithelial cell maturation involved in salivary gland development / positive regulation of vascular wound healing / positive regulation of protein acetylation / ATF6-mediated unfolded protein response / negative regulation of striated muscle cell apoptotic process / regulation of skeletal muscle fiber development / glandular epithelial cell maturation / sterol homeostasis / positive regulation of cell proliferation involved in heart morphogenesis / IRE1alpha activates chaperones ...epithelial cell maturation involved in salivary gland development / positive regulation of vascular wound healing / positive regulation of protein acetylation / ATF6-mediated unfolded protein response / negative regulation of striated muscle cell apoptotic process / regulation of skeletal muscle fiber development / glandular epithelial cell maturation / sterol homeostasis / positive regulation of cell proliferation involved in heart morphogenesis / IRE1alpha activates chaperones / positive regulation of skeletal muscle tissue growth / ATF6 (ATF6-alpha) activates chaperone genes / positive regulation of plasma cell differentiation / positive regulation of phospholipid biosynthetic process / negative regulation of myotube differentiation / negative regulation of protein localization to endoplasmic reticulum / nascent polypeptide-associated complex / positive regulation of ERAD pathway / intracellular triglyceride homeostasis / cardiac ventricle development / cellular response to fructose stimulus / positive regulation of lactation / cellular response to laminar fluid shear stress / XBP1(S) activates chaperone genes / heart trabecula morphogenesis / cellular response to nutrient / skeletal muscle tissue regeneration / positive regulation of hepatocyte proliferation / cellular response to fluid shear stress / positive regulation of MHC class II biosynthetic process / embryonic brain development / translation at presynapse / exocrine pancreas development / exit from mitosis / optic nerve development / response to insecticide / regulation of translation involved in cellular response to UV / endothelial cell proliferation / positive regulation of cytokine production involved in inflammatory response / positive regulation of vascular associated smooth muscle cell migration / eukaryotic 80S initiation complex / ribosomal protein import into nucleus / negative regulation of formation of translation preinitiation complex / negative regulation of endoplasmic reticulum unfolded protein response / axial mesoderm development / regulation of G1 to G0 transition / retinal ganglion cell axon guidance / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein-DNA complex disassembly / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / 90S preribosome assembly / positive regulation of ubiquitin-protein transferase activity / protein tyrosine kinase inhibitor activity / positive regulation of DNA-templated transcription initiation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / alpha-beta T cell differentiation / nucleolus organization / TNFR1-mediated ceramide production / positive regulation of DNA damage response, signal transduction by p53 class mediator / GAIT complex / cellular response to peptide hormone stimulus / negative regulation of RNA splicing / positive regulation of B cell differentiation / TORC2 complex binding / positive regulation of T cell differentiation / muscle organ development / neural crest cell differentiation / supercoiled DNA binding / G1 to G0 transition / cytoplasmic translational initiation / NF-kappaB complex / negative regulation of DNA repair / middle ear morphogenesis / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / rRNA modification in the nucleus and cytosol / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / positive regulation of immunoglobulin production / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / IRE1-mediated unfolded protein response / regulation of establishment of cell polarity / negative regulation of phagocytosis / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / Formation of the ternary complex, and subsequently, the 43S complex / negative regulation of SMAD protein signal transduction / ion channel inhibitor activity / protein kinase A binding / laminin receptor activity / homeostatic process / pigmentation / Ribosomal scanning and start codon recognition / positive regulation of mitochondrial depolarization Similarity search - Function
: / Nascent polypeptide-associated complex subunit alpha / Nascent polypeptide-associated complex subunit alpha-like, UBA domain / HYPK UBA domain / Transcription factor BTF3 / Nascent polypeptide-associated complex NAC domain / NAC A/B domain superfamily / NAC domain / NAC A/B domain profile. / NAC ...: / Nascent polypeptide-associated complex subunit alpha / Nascent polypeptide-associated complex subunit alpha-like, UBA domain / HYPK UBA domain / Transcription factor BTF3 / Nascent polypeptide-associated complex NAC domain / NAC A/B domain superfamily / NAC domain / NAC A/B domain profile. / NAC / Basic region leucine zipper / Basic-leucine zipper (bZIP) domain signature. / Basic-leucine zipper (bZIP) domain profile. / basic region leucin zipper / Basic-leucine zipper domain / Basic-leucine zipper domain superfamily / 60s Acidic ribosomal protein / 60S acidic ribosomal protein P0 / : / 40S ribosomal protein SA / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / 40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ubiquitin-like protein FUBI / 50S ribosomal protein L10, insertion domain superfamily / 60S ribosomal protein L10P, insertion domain / Insertion domain in 60S ribosomal protein L10P / Ribosomal protein L30e / Ribosomal L15/L27a, N-terminal / Ribosomal protein L28e / : / Ribosomal protein L23 / Ribosomal protein L2, archaeal-type / Ribosomal L28e/Mak16 / Ribosomal L28e protein family / metallochaperone-like domain / TRASH domain / : / Ribosomal protein S26e signature. / Ribosomal protein L41 / Ribosomal protein L41 / Ribosomal protein S21e, conserved site / Ribosomal protein S21e signature. / Ribosomal protein L13e, conserved site / Ribosomal protein L13e signature. / : / Ribosomal protein S12e signature. / Ribosomal protein S12e / Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S26e / Ribosomal protein L29e / Ribosomal L29e protein family / Ribosomal protein L27e, conserved site / Ribosomal protein L27e signature. / Ribosomal protein L22e / Ribosomal protein L22e superfamily / Ribosomal L22e protein family / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein L13e / Ribosomal protein S5, eukaryotic/archaeal / Ribosomal protein L13e / Ribosomal protein S21e / Ribosomal protein L38e / Ribosomal protein L38e superfamily / Ribosomal protein S21e superfamily / Ribosomal protein S21e / Ribosomal L38e protein family / Ribosomal protein S19e, conserved site / Ribosomal protein S19e signature. / Ribosomal protein S2, eukaryotic / Ribosomal protein L19, eukaryotic / : / Ribosomal protein L10e, conserved site / Ribosomal protein L6e signature. / Ribosomal protein L10e signature. / Ribosomal protein L19/L19e conserved site / Ribosomal protein L19e signature. / Ribosomal protein L44e signature. / 60S ribosomal protein L18a/ L20, eukaryotes / 40S Ribosomal protein S10 / Ribosomal protein L10e / Ribosomal protein L24e, conserved site / Ribosomal protein L24e signature. / Ribosomal protein L18/L18-A/B/e, conserved site / Ribosomal protein L18e signature. / S27a-like superfamily / Ribosomal protein L34e, conserved site / Ribosomal protein L34e signature. / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein L5 eukaryotic, C-terminal / Ribosomal L18 C-terminal region / Ribosomal protein L23/L25, N-terminal / Ribosomal protein L23, N-terminal domain / : / Ribosomal L40e family / Ribosomal protein L36e signature. / Ribosomal protein S30 Similarity search - Domain/homology
Large ribosomal subunit protein uL10 / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Small ribosomal subunit protein uS5 / X-box-binding protein 1 / Large ribosomal subunit protein eL33 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL22 / Transcription factor BTF3 / Small ribosomal subunit protein uS3 ...Large ribosomal subunit protein uL10 / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Small ribosomal subunit protein uS5 / X-box-binding protein 1 / Large ribosomal subunit protein eL33 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL22 / Transcription factor BTF3 / Small ribosomal subunit protein uS3 / Small ribosomal subunit protein eS12 / Large ribosomal subunit protein eL13 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein uL11 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein eL22 / Large ribosomal subunit protein uL4 / Small ribosomal subunit protein eS19 / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein uL13 / Small ribosomal subunit protein eS27 / Large ribosomal subunit protein uL29 / Large ribosomal subunit protein uL15 / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein eL21 / Large ribosomal subunit protein eL28 / Small ribosomal subunit protein uS4 / Small ribosomal subunit protein uS7 / Small ribosomal subunit protein eS10 / Large ribosomal subunit protein eL29 / Large ribosomal subunit protein eL34 / Large ribosomal subunit protein eL14 / Small ribosomal subunit protein uS10 / Small ribosomal subunit protein eS1 / Large ribosomal subunit protein uL24 / Large ribosomal subunit protein eL15 / Large ribosomal subunit protein eL27 / Large ribosomal subunit protein eL43 / Large ribosomal subunit protein eL37 / Small ribosomal subunit protein eS7 / Small ribosomal subunit protein eS8 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein uS9 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS12 / Small ribosomal subunit protein uS13 / Small ribosomal subunit protein uS14 / Small ribosomal subunit protein uS15 / Small ribosomal subunit protein uS17 / Large ribosomal subunit protein eL8 / Small ribosomal subunit protein eS4, X isoform / Large ribosomal subunit protein uL23 / Small ribosomal subunit protein eS6 / Large ribosomal subunit protein uL14 / Small ribosomal subunit protein uS19 / Small ribosomal subunit protein eS24 / Small ribosomal subunit protein eS25 / Small ribosomal subunit protein eS26 / Small ribosomal subunit protein eS28 / Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein / Large ribosomal subunit protein eL30 / Large ribosomal subunit protein eL39 / Large ribosomal subunit protein eL31 / Large ribosomal subunit protein eL32 / Large ribosomal subunit protein uL5 / Large ribosomal subunit protein uL2 / Small ribosomal subunit protein eS32 / Ubiquitin-ribosomal protein eS31 fusion protein / Ubiquitin-ribosomal protein eL40 fusion protein / Large ribosomal subunit protein eL38 / Small ribosomal subunit protein eS21 / Small ribosomal subunit protein RACK1 / Large ribosomal subunit protein eL24 / Large ribosomal subunit protein eL42 / Large ribosomal subunit protein eL19 / Large ribosomal subunit protein eL20 / Large ribosomal subunit protein eL6 / Large ribosomal subunit protein eL18 / Nascent polypeptide-associated complex subunit alpha / Large ribosomal subunit protein eL36 Similarity search - Component
Biological species
Homo sapiens (human)
Method
single particle reconstruction / cryo EM / Resolution: 2.7 Å
European Union, Germany, United States, Switzerland, 7 items
Organization
Grant number
Country
European Research Council (ERC)
SyG-101072047
European Union
German Research Foundation (DFG)
KR3593/4-1
Germany
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35 GM136321
United States
National Science Foundation (NSF, United States)
2219287
United States
Swiss National Science Foundation
310030_212308
Switzerland
European Molecular Biology Organization (EMBO)
European Union
Boehringer Ingelheim Fonds (BIF)
Germany
Citation
Journal: Mol Cell / Year: 2026 Title: NAC promotes co-translational protein folding at the ribosomal tunnel exit. Authors: 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 ...Authors: 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 / 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 ...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.
Entire : XBP1u-stalled RPL4 RNC in complex with NAC
Entire
Name: XBP1u-stalled RPL4 RNC in complex with NAC
Components
Complex: XBP1u-stalled RPL4 RNC in complex with NAC
Protein or peptide: 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
RNA: tRNA-Met-CAT
RNA: mRNA fragment (6-MER)
RNA: 28S rRNA
RNA: 5S rRNA
RNA: 5.8S rRNA
Protein or peptide: Large ribosomal subunit protein uL2
Protein or peptide: Large ribosomal subunit protein uL3
Protein or peptide: 60S ribosomal protein L4
Protein or peptide: 60S ribosomal protein L5
Protein or peptide: Large ribosomal subunit protein eL6
Protein or peptide: Large ribosomal subunit protein uL30
Protein or peptide: 60S ribosomal protein L7a
Protein or peptide: 60S ribosomal protein L9
Protein or peptide: 60S ribosomal protein L10
Protein or peptide: 60S ribosomal protein L11
Protein or peptide: 60S ribosomal protein L13
Protein or peptide: 60S ribosomal protein L14
Protein or peptide: 60S ribosomal protein L15
Protein or peptide: 60S ribosomal protein L13a
Protein or peptide: 60S ribosomal protein L17
Protein or peptide: 60S ribosomal protein L18
Protein or peptide: 60S ribosomal protein L19
Protein or peptide: 60S ribosomal protein L18a
Protein or peptide: 60S ribosomal protein L21
Protein or peptide: 60S ribosomal protein L22
Protein or peptide: 60S ribosomal protein L23
Protein or peptide: 60S ribosomal protein L24
Protein or peptide: 60S ribosomal protein L23a
Protein or peptide: 60S ribosomal protein L26
Protein or peptide: 60S ribosomal protein L27
Protein or peptide: Large ribosomal subunit protein uL15
Protein or peptide: Large ribosomal subunit protein eL29
Protein or peptide: 60S ribosomal protein L30
Protein or peptide: 60S ribosomal protein L31
Protein or peptide: 60S ribosomal protein L32
Protein or peptide: 60S ribosomal protein L35a
Protein or peptide: 60S ribosomal protein L34
Protein or peptide: 60S ribosomal protein L35
Protein or peptide: 60S ribosomal protein L36
Protein or peptide: Large ribosomal subunit protein eL37
Protein or peptide: 60S ribosomal protein L38
Protein or peptide: 60S ribosomal protein L39
Protein or peptide: Ubiquitin-60S ribosomal protein L40
Protein or peptide: Large ribosomal subunit protein eL42
Protein or peptide: 60S ribosomal protein L37a
Protein or peptide: Large ribosomal subunit protein eL28
Protein or peptide: 60S acidic ribosomal protein P0
Protein or peptide: Large ribosomal subunit protein uL11
Protein or peptide: Nascent polypeptide-associated complex subunit alpha
Protein or peptide: Transcription factor BTF3
RNA: 18S rRNA
Protein or peptide: Small ribosomal subunit protein uS2
Protein or peptide: 40S ribosomal protein S3a
Protein or peptide: 40S ribosomal protein S2
Protein or peptide: 40S ribosomal protein S3
Protein or peptide: Small ribosomal subunit protein eS4, X isoform
Protein or peptide: 40S ribosomal protein S5
Protein or peptide: 40S ribosomal protein S6
Protein or peptide: 40S ribosomal protein S7
Protein or peptide: 40S ribosomal protein S8
Protein or peptide: 40S ribosomal protein S9
Protein or peptide: 40S ribosomal protein S10
Protein or peptide: Small ribosomal subunit protein uS17
Protein or peptide: 40S ribosomal protein S12
Protein or peptide: 40S ribosomal protein S13
Protein or peptide: 40S ribosomal protein S14
Protein or peptide: 40S ribosomal protein S15
Protein or peptide: 40S ribosomal protein S16
Protein or peptide: 40S ribosomal protein S17
Protein or peptide: Small ribosomal subunit protein uS13
Protein or peptide: Small ribosomal subunit protein eS19
Protein or peptide: 40S ribosomal protein S20
Protein or peptide: Small ribosomal subunit protein eS21
Protein or peptide: 40S ribosomal protein S15a
Protein or peptide: Small ribosomal subunit protein uS12
Protein or peptide: 40S ribosomal protein S24
Protein or peptide: Small ribosomal subunit protein eS25
Protein or peptide: 40S ribosomal protein S26
Protein or peptide: 40S ribosomal protein S27
Protein or peptide: 40S ribosomal protein S28
Protein or peptide: 40S ribosomal protein S29
Protein or peptide: Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein
Protein or peptide: Ubiquitin
Protein or peptide: Receptor of activated protein C kinase 1
Protein or peptide: 60S ribosomal protein L41
Ligand: MAGNESIUM ION
Ligand: ZINC ION
+
Supramolecule #1: XBP1u-stalled RPL4 RNC in complex with NAC
Macromolecule #41: Large ribosomal subunit protein eL37
Macromolecule
Name: Large ribosomal subunit protein eL37 / type: protein_or_peptide / ID: 41 / Details: zinc binding protein / Number of copies: 1 / Enantiomer: LEVO
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