negative regulation of protein localization to endoplasmic reticulum / nascent polypeptide-associated complex / negative regulation of striated muscle cell apoptotic process / regulation of skeletal muscle fiber development / positive regulation of cell proliferation involved in heart morphogenesis / positive regulation of skeletal muscle tissue growth / cardiac ventricle development / glucose-6-phosphate isomerase / N-terminal protein amino acid modification / glucose-6-phosphate isomerase activity ...negative regulation of protein localization to endoplasmic reticulum / nascent polypeptide-associated complex / negative regulation of striated muscle cell apoptotic process / regulation of skeletal muscle fiber development / positive regulation of cell proliferation involved in heart morphogenesis / positive regulation of skeletal muscle tissue growth / cardiac ventricle development / glucose-6-phosphate isomerase / N-terminal protein amino acid modification / glucose-6-phosphate isomerase activity / peptidyl-methionine modification / hemostasis / glucose 6-phosphate metabolic process / methionyl aminopeptidase / initiator methionyl aminopeptidase activity / heart trabecula morphogenesis / carbohydrate derivative binding / skeletal muscle tissue regeneration / metalloexopeptidase activity / Gluconeogenesis / monosaccharide binding / fructose 6-phosphate metabolic process / ribosomal subunit / Glycolysis / exit from mitosis / erythrocyte homeostasis / ciliary membrane / optic nerve development / positive regulation of immunoglobulin production / laminin receptor activity / retinal ganglion cell axon guidance / organelle membrane / metalloaminopeptidase activity / response to testosterone / humoral immune response / Peptide chain elongation / mesoderm formation / Selenocysteine synthesis / response to immobilization stress / positive regulation of signal transduction by p53 class mediator / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / Viral mRNA Translation / phagocytic cup / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / 90S preribosome / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / aminopeptidase activity / Major pathway of rRNA processing in the nucleolus and cytosol / protein-RNA complex assembly / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / response to cadmium ion / maturation of LSU-rRNA / ribosomal small subunit export from nucleus / rough endoplasmic reticulum / laminin binding / translation regulator activity / gastrulation / response to muscle stretch / MDM2/MDM4 family protein binding / cytosolic ribosome / positive regulation of endothelial cell migration / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / protein maturation / cellular response to interleukin-4 / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / response to progesterone / ribosomal large subunit biogenesis / positive regulation of apoptotic signaling pathway / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / cytokine activity / gluconeogenesis / glycolytic process / TP53 Regulates Metabolic Genes / maturation of SSU-rRNA / small-subunit processome / growth factor activity / wound healing / spindle / platelet aggregation / mRNA 5'-UTR binding / Regulation of expression of SLITs and ROBOs / cytoplasmic ribonucleoprotein granule / antimicrobial humoral immune response mediated by antimicrobial peptide / rRNA processing / rhythmic process / positive regulation of canonical Wnt signaling pathway / Inactivation, recovery and regulation of the phototransduction cascade / glucose homeostasis / protein transport / response to estradiol / regulation of translation / large ribosomal subunit / heparin binding / ribosome binding Similarity search - Function
Transcription factor BTF3 / Nascent polypeptide-associated complex NAC domain / Nascent polypeptide-associated complex subunit alpha / NAC A/B domain superfamily / NAC domain / NAC A/B domain profile. / NAC / Nascent polypeptide-associated complex subunit alpha-like, UBA domain / HYPK UBA domain / MYND-like zinc finger ...Transcription factor BTF3 / Nascent polypeptide-associated complex NAC domain / Nascent polypeptide-associated complex subunit alpha / NAC A/B domain superfamily / NAC domain / NAC A/B domain profile. / NAC / Nascent polypeptide-associated complex subunit alpha-like, UBA domain / HYPK UBA domain / MYND-like zinc finger / zf-MYND-like zinc finger, mRNA-binding / Zinc finger C6H2-type profile. / Phosphoglucose isomerase, C-terminal / Phosphoglucose isomerase signature 1. / Phosphoglucose isomerase (PGI) / Phosphoglucose isomerase, conserved site / Phosphoglucose isomerase, SIS domain 1 / Phosphoglucose isomerase, SIS domain 2 / Phosphoglucose isomerase / Phosphoglucose isomerase signature 2. / Glucose-6-phosphate isomerase family profile. / Methionine aminopeptidase subfamily 1 signature. / Peptidase M24A, methionine aminopeptidase, subfamily 1 / SIS domain superfamily / Peptidase M24, methionine aminopeptidase / 60s Acidic ribosomal protein / 60S acidic ribosomal protein P0 / : / 40S ribosomal protein SA / Peptidase M24 / Metallopeptidase family M24 / 40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Creatinase/aminopeptidase-like / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ubiquitin-like protein FUBI / Ribosomal protein L30e / Ribosomal protein L2, archaeal-type / Ribosomal L15/L27a, N-terminal / Ribosomal protein L28e / 50S ribosomal protein L10, insertion domain superfamily / Ribosomal protein L23 / 60S ribosomal protein L10P, insertion domain / Insertion domain in 60S ribosomal protein L10P / 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 L1, conserved site / Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S26e / Ribosomal protein L1 signature. / : / Ribosomal protein S12e signature. / Ribosomal protein L1 / Ribosomal protein S12e / Ribosomal protein L29e / Ribosomal L29e protein family / Ribosomal protein S19e, conserved site / Ribosomal protein S19e signature. / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein S5, eukaryotic/archaeal / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e / Ribosomal protein S2, eukaryotic / S27a-like superfamily / Ribosomal protein L22e / Ribosomal protein L22e superfamily / Ribosomal L22e protein family / Ribosomal protein L10e, conserved site / Ribosomal protein L10e signature. / Ribosomal protein L27e, conserved site / Ribosomal protein L27e signature. / Ribosomal protein L10e / 40S Ribosomal protein S10 / Ribosomal protein L38e / Ribosomal protein L38e superfamily / Ribosomal L38e protein family / : / Ribosomal protein S7e signature. / Ribosomal protein L44e signature. / Ribosomal protein L1, 3-layer alpha/beta-sandwich / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein L24e, conserved site / Ribosomal protein L24e signature. / : / Ribosomal protein S10, eukaryotic/archaeal / Ribosomal protein L19, eukaryotic / Ribosomal protein L19/L19e conserved site / Ribosomal protein L19e signature. Similarity search - Domain/homology
Small ribosomal subunit protein eS32 / Large ribosomal subunit protein uL13 / Small ribosomal subunit protein eS21 / Large ribosomal subunit protein eL20 / Ubiquitin-ribosomal protein eL40 fusion protein / 40S ribosomal protein S26 / Transcription factor BTF3 / Large ribosomal subunit protein uL16 / Small ribosomal subunit protein uS4 / Large ribosomal subunit protein uL2 ...Small ribosomal subunit protein eS32 / Large ribosomal subunit protein uL13 / Small ribosomal subunit protein eS21 / Large ribosomal subunit protein eL20 / Ubiquitin-ribosomal protein eL40 fusion protein / 40S ribosomal protein S26 / Transcription factor BTF3 / Large ribosomal subunit protein uL16 / Small ribosomal subunit protein uS4 / Large ribosomal subunit protein uL2 / Large ribosomal subunit protein uL15/eL18 domain-containing protein / Large ribosomal subunit protein eL24 / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein eL33 / Small ribosomal subunit protein eS12 / Large ribosomal subunit protein eL29 / Small ribosomal subunit protein uS9 / Large ribosomal subunit protein eL31 / Large ribosomal subunit protein eL21 / Large ribosomal subunit protein uL29 / Small ribosomal subunit protein uS10 / Small ribosomal subunit protein RACK1 / Ubiquitin-ribosomal protein eS31 fusion protein / Large ribosomal subunit protein eL6 / Large ribosomal subunit protein uL1 / Large ribosomal subunit protein uL11 / Large ribosomal subunit protein uL15 / Small ribosomal subunit protein uS15 / Large ribosomal subunit protein uL10 / Large ribosomal subunit protein uL24 / Small ribosomal subunit protein eS1 / Small ribosomal subunit protein eS7 / Large ribosomal subunit protein uL4 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein eL43 / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein eL14 / Small ribosomal subunit protein uS12 / Large ribosomal subunit protein eL15 / 40S ribosomal protein S24 / Large ribosomal subunit protein uL14 / Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein / Small ribosomal subunit protein eS25 / Large ribosomal subunit protein eL30 / Small ribosomal subunit protein uS7 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein eS28 / Small ribosomal subunit protein eS8 / Small ribosomal subunit protein eS4 / Large ribosomal subunit protein eL13 / Large ribosomal subunit protein uL3 / Small ribosomal subunit protein uS2 / Small ribosomal subunit protein eS6 / Small ribosomal subunit protein eS19 / Small ribosomal subunit protein uS3 / Small ribosomal subunit protein uS13 / Small ribosomal subunit protein eS10 / Small ribosomal subunit protein uS17 / Large ribosomal subunit protein eL22 / Large ribosomal subunit protein eL39 / Large ribosomal subunit protein eL36 / Small ribosomal subunit protein eS17 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL5 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein eL27 / Large ribosomal subunit protein eL34 / Large ribosomal subunit protein eL19 / Small ribosomal subunit protein eS27 / Large ribosomal subunit protein eL38 / Small ribosomal subunit protein uS19 / Large ribosomal subunit protein eL42 / Large ribosomal subunit protein eL32 / Small ribosomal subunit protein uS11 / Large ribosomal subunit protein eL28 / Small ribosomal subunit protein uS14 / Small ribosomal subunit protein uS5 / Glucose-6-phosphate isomerase / Methionine aminopeptidase 1 / Large ribosomal subunit protein eL8 / Nascent polypeptide-associated complex subunit alpha / Large ribosomal subunit protein eL37 Similarity search - Component
Biological species
Oryctolagus cuniculus (rabbit) / Homo sapiens (human)
Method
single particle reconstruction / cryo EM / Resolution: 2.9 Å
Journal: Science / Year: 2023 Title: NAC controls cotranslational N-terminal methionine excision in eukaryotes. Authors: Martin Gamerdinger / Min Jia / Renate Schloemer / Laurenz Rabl / Mateusz Jaskolowski / Katrin M Khakzar / Zeynel Ulusoy / Annalena Wallisch / Ahmad Jomaa / Gundula Hunaeus / Alain Scaiola / ...Authors: Martin Gamerdinger / Min Jia / Renate Schloemer / Laurenz Rabl / Mateusz Jaskolowski / Katrin M Khakzar / Zeynel Ulusoy / Annalena Wallisch / Ahmad Jomaa / Gundula Hunaeus / Alain Scaiola / Kay Diederichs / Nenad Ban / Elke Deuerling / Abstract: N-terminal methionine excision from newly synthesized proteins, catalyzed cotranslationally by methionine aminopeptidases (METAPs), is an essential and universally conserved process that plays a key ...N-terminal methionine excision from newly synthesized proteins, catalyzed cotranslationally by methionine aminopeptidases (METAPs), is an essential and universally conserved process that plays a key role in cell homeostasis and protein biogenesis. However, how METAPs interact with ribosomes and how their cleavage specificity is ensured is unknown. We discovered that in eukaryotes the nascent polypeptide-associated complex (NAC) controls ribosome binding of METAP1. NAC recruits METAP1 using a long, flexible tail and provides a platform for the formation of an active methionine excision complex at the ribosomal tunnel exit. This mode of interaction ensures the efficient excision of methionine from cytosolic proteins, whereas proteins targeted to the endoplasmic reticulum are spared. Our results suggest a broader mechanism for how access of protein biogenesis factors to translating ribosomes is controlled.
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