N-terminal L-serine Nalpha-acetyltransferase NatD / histone H2A acetyltransferase activity / negative regulation of striated muscle cell apoptotic process / regulation of skeletal muscle fiber development / positive regulation of cell proliferation involved in heart morphogenesis / protein N-terminal-serine acetyltransferase activity / positive regulation of skeletal muscle tissue growth / negative regulation of protein localization to endoplasmic reticulum / nascent polypeptide-associated complex / cardiac ventricle development ...N-terminal L-serine Nalpha-acetyltransferase NatD / histone H2A acetyltransferase activity / negative regulation of striated muscle cell apoptotic process / regulation of skeletal muscle fiber development / positive regulation of cell proliferation involved in heart morphogenesis / protein N-terminal-serine acetyltransferase activity / positive regulation of skeletal muscle tissue growth / negative regulation of protein localization to endoplasmic reticulum / nascent polypeptide-associated complex / cardiac ventricle development / SUMO is conjugated to E1 (UBA2:SAE1) / SUMOylation of nuclear envelope proteins / SUMO is transferred from E1 to E2 (UBE2I, UBC9) / SUMO is proteolytically processed / SUMOylation of transcription factors / Postmitotic nuclear pore complex (NPC) reformation / SUMOylation of transcription cofactors / septin ring / SUMOylation of DNA damage response and repair proteins / Transcriptional and post-translational regulation of MITF-M expression and activity / SUMOylation of DNA replication proteins / histone H4 acetyltransferase activity / methionyl aminopeptidase / initiator methionyl aminopeptidase activity / heart trabecula morphogenesis / skeletal muscle tissue regeneration / embryonic brain development / metalloexopeptidase activity / translation at presynapse / SUMOylation of SUMOylation proteins / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / exit from mitosis / optic nerve development / eukaryotic 80S initiation complex / negative regulation of protein neddylation / regulation of translation involved in cellular response to UV / SUMOylation of RNA binding proteins / axial mesoderm development / negative regulation of formation of translation preinitiation complex / regulation of G1 to G0 transition / retinal ganglion cell axon guidance / oxidized pyrimidine DNA binding / response to TNF agonist / negative regulation of endoplasmic reticulum unfolded protein response / positive regulation of base-excision repair / ribosomal protein import into nucleus / protein-DNA complex disassembly / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / 90S preribosome assembly / protein tyrosine kinase inhibitor activity / SUMOylation of chromatin organization proteins / positive regulation of endodeoxyribonuclease activity / nucleolus organization / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / alpha-beta T cell differentiation / negative regulation of DNA repair / negative regulation of RNA splicing / GAIT complex / positive regulation of DNA damage response, signal transduction by p53 class mediator / TORC2 complex binding / G1 to G0 transition / supercoiled DNA binding / NF-kappaB complex / neural crest cell differentiation / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / middle ear morphogenesis / positive regulation of ubiquitin-protein transferase activity / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of bicellular tight junction assembly / muscle organ development / regulation of establishment of cell polarity / ubiquitin-like protein conjugating enzyme binding / rRNA modification in the nucleus and cytosol / negative regulation of phagocytosis / erythrocyte homeostasis / Formation of the ternary complex, and subsequently, the 43S complex / cytoplasmic side of rough endoplasmic reticulum membrane / negative regulation of ubiquitin protein ligase activity / protein kinase A binding / laminin receptor activity / homeostatic process / ion channel inhibitor activity / Ribosomal scanning and start codon recognition / metalloaminopeptidase activity / pigmentation / Translation initiation complex formation / positive regulation of mitochondrial depolarization / macrophage chemotaxis / lung morphogenesis / positive regulation of T cell receptor signaling pathway / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / positive regulation of natural killer cell proliferation / ubiquitin-like protein ligase binding Similarity search - Function
N-alpha-acetyltransferase 40 / : / Nascent polypeptide-associated complex subunit alpha / 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. / Transcription factor BTF3 / Nascent polypeptide-associated complex NAC domain ...N-alpha-acetyltransferase 40 / : / Nascent polypeptide-associated complex subunit alpha / 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. / Transcription factor BTF3 / Nascent polypeptide-associated complex NAC domain / NAC A/B domain superfamily / NAC domain / NAC A/B domain profile. / NAC / Methionine aminopeptidase subfamily 1 signature. / Peptidase M24A, methionine aminopeptidase, subfamily 1 / Basic region leucine zipper / Rad60/SUMO-like domain / Ubiquitin-2 like Rad60 SUMO-like / Peptidase M24, methionine aminopeptidase / 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 / Peptidase M24 / Metallopeptidase family M24 / Creatinase/aminopeptidase-like / 40S ribosomal protein SA / Acetyltransferase (GNAT) family / 40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ubiquitin-like protein FUBI / Ribosomal protein L30e / Ribosomal protein L28e / Ribosomal L15/L27a, N-terminal / Ribosomal protein L23 / Gcn5-related N-acetyltransferase (GNAT) domain profile. / Ribosomal protein L2, archaeal-type / Ribosomal L28e/Mak16 / Ribosomal L28e protein family / GNAT domain / 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 S26e / Ribosomal protein S26e superfamily / Ribosomal protein S26e / Ribosomal protein S12e / Ribosomal protein L29e / Ribosomal L29e protein family / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein L27e, conserved site / Ribosomal protein L27e signature. / Ribosomal protein L22e / Ribosomal protein L22e superfamily / Ribosomal L22e protein family / Ribosomal protein S21e / Ribosomal protein S5, eukaryotic/archaeal / Ribosomal protein S21e superfamily / Ribosomal protein S21e / Ribosomal protein S19e, conserved site / Ribosomal protein S19e signature. / Ribosomal protein S2, eukaryotic / Ribosomal protein L38e / Ribosomal protein L38e superfamily / Ribosomal L38e protein family / Ribosomal protein L13e / Ribosomal protein L13e / Ribosomal protein L19, eukaryotic / S27a-like superfamily / Ribosomal protein L10e, conserved site / : / Ribosomal protein L44e signature. / Ribosomal protein L10e signature. / Ribosomal protein L19/L19e conserved site / 40S Ribosomal protein S10 / Ribosomal protein L19e signature. / Ribosomal protein L6e signature. / 60S ribosomal protein L18a/ L20, eukaryotes / Ribosomal protein L24e, conserved site / Ribosomal protein L24e signature. / Ribosomal protein L10e / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein L18/L18-A/B/e, conserved site / Ribosomal protein L18e signature. / Ribosomal protein L34e, conserved site / Ribosomal protein L34e signature. Similarity search - Domain/homology
X-box-binding protein 1 / 40S ribosomal protein S15 / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Small ribosomal subunit protein uS5 / Large ribosomal subunit protein eL33 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein uL22 / Transcription factor BTF3 / Small ribosomal subunit protein uS3 ...X-box-binding protein 1 / 40S ribosomal protein S15 / Small ribosomal subunit protein eS17 / Small ribosomal subunit protein uS2 / Small ribosomal subunit protein uS5 / 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 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 / Green fluorescent protein / 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 / Methionine aminopeptidase 1 / Small ubiquitin-related modifier 1 / 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 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 / 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 / Ubiquitin-like protein SMT3 / Nascent polypeptide-associated complex subunit alpha / N-alpha-acetyltransferase 40 / Large ribosomal subunit protein eL36 Similarity search - Component
Biological species
Homo sapiens (human)
Method
single particle reconstruction / cryo EM / Resolution: 3.55 Å
European Union, Switzerland, Germany, United States, 5 items
Organization
Grant number
Country
European Research Council (ERC)
101072047
European Union
Swiss National Science Foundation
310030_212308
Switzerland
Swiss National Science Foundation
51NF40-205601
Switzerland
German Research Foundation (DFG)
537004599
Germany
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35 GM136321
United States
Citation
Journal: Sci Adv / Year: 2025 Title: Mechanism of cotranslational modification of histones H2A and H4 by MetAP1 and NatD. Authors: Denis Yudin / Mateusz Jaskolowski / Ziyi Fan / Nicolas Burg / Sowmya Chandrasekar / Alfred M Lentzsch / Alain Scaiola / Adrian Bothe / Elke Deuerling / Martin Gamerdinger / Shu-Ou Shan / Nenad Ban / Abstract: The replication-dependent histones H2A and H4 are among the most highly expressed proteins in eukaryotes during the S phase to ensure packaging of replicated chromosomes. Nearly all newly synthesized ...The replication-dependent histones H2A and H4 are among the most highly expressed proteins in eukaryotes during the S phase to ensure packaging of replicated chromosomes. Nearly all newly synthesized H2A and H4 are N-terminally acetylated by N-terminal acetyltransferase D (NatD) following excision of the initiator methionine by methionine aminopeptidases (MetAPs). These modifications influence chromatin function, but how they occur cotranslationally on these exceptionally abundant and small proteins was not understood. Here, we show that the nascent polypeptide-associated complex controls the cotranslational modification of histones H2A and H4 by recruiting NatD and the upstream enzyme MetAP1 to ribosomes. MetAP1 and NatD cooperate on the ribosome to create a confined environment for the efficient sequential modification of the nascent histone chain. Our work provides a mechanistic model for the early steps of histone maturation.
Entire : Human quaternary complex of a translating 80S ribosome, NAC, MetA...
Entire
Name: Human quaternary complex of a translating 80S ribosome, NAC, MetAP1 and NatD
Components
Complex: Human quaternary complex of a translating 80S ribosome, NAC, MetAP1 and NatD
Complex: 60S subunit
RNA: 28S rRNA
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 uL13
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: 60S ribosomal protein L27a
Protein or peptide: 60S ribosomal protein L29
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
RNA: 5S rRNA
RNA: 5.8S rRNA
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: 60S ribosomal protein L36a
Protein or peptide: 60S ribosomal protein L37a
Protein or peptide: 60S ribosomal protein L28
Protein or peptide: 60S ribosomal protein L15
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: Large ribosomal subunit protein eL13
Protein or peptide: 60S ribosomal protein L14
Protein or peptide: 60S ribosomal protein L8
Protein or peptide: 60S ribosomal protein L3
Complex: 40S subunit
Protein or peptide: 40S ribosomal protein S8
Protein or peptide: 40S ribosomal protein S9
Protein or peptide: 40S ribosomal protein S5
Protein or peptide: 40S ribosomal protein S11
Protein or peptide: 40S ribosomal protein S10
Protein or peptide: 40S ribosomal protein S13
Protein or peptide: 40S ribosomal protein S14
Protein or peptide: 40S ribosomal protein S12
Protein or peptide: 40S ribosomal protein S15
Protein or peptide: 40S ribosomal protein S17
Protein or peptide: 40S ribosomal protein S16
Protein or peptide: Small ribosomal subunit protein uS13
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: Isoform 3 of Small ribosomal subunit protein eS24
Protein or peptide: Small ribosomal subunit protein eS19
Protein or peptide: 40S ribosomal protein S26
Protein or peptide: 40S ribosomal protein S27
Protein or peptide: 40S ribosomal protein S20
Protein or peptide: 40S ribosomal protein S25
Protein or peptide: Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein
Protein or peptide: 40S ribosomal protein S28
Protein or peptide: 40S ribosomal protein S29
Protein or peptide: 60S ribosomal protein L41
Protein or peptide: Ubiquitin
Protein or peptide: Receptor of activated protein C kinase 1
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: Small ribosomal subunit protein eS4, X isoform
Protein or peptide: 40S ribosomal protein S3
Protein or peptide: 40S ribosomal protein S6
Protein or peptide: 40S ribosomal protein S7
Complex: mRNA
RNA: mRNA
Complex: tRNA
RNA: tRNA
Complex: nascent chain
Protein or peptide: Green fluorescent protein,Small ubiquitin-related modifier 1,Green fluorescent protein,Small ubiquitin-related modifier 1,Histone H4,X-box-binding protein 1,X-box-binding protein 1
Complex: NAC
Protein or peptide: Nascent polypeptide-associated complex subunit alpha
Protein or peptide: Isoform 2 of Transcription factor BTF3
Complex: MetAP1
Protein or peptide: Methionine aminopeptidase 1
Complex: NatD
Protein or peptide: Ubiquitin-like protein SMT3,N-alpha-acetyltransferase 40
RNA: 18S rRNA
Ligand: ZINC ION
Ligand: COENZYME A
Ligand: GUANOSINE-5'-TRIPHOSPHATE
+
Supramolecule #1: Human quaternary complex of a translating 80S ribosome, NAC, MetA...
Supramolecule
Name: Human quaternary complex of a translating 80S ribosome, NAC, MetAP1 and NatD type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#86
Model: Quantifoil R2/2 / Material: COPPER / Mesh: 300 / Support film - #0 - Film type ID: 1 / Support film - #0 - Material: CARBON / Support film - #0 - topology: HOLEY / Support film - #1 - Film type ID: 2 / Support film - #1 - Material: CARBON / Support film - #1 - topology: CONTINUOUS / Pretreatment - Type: GLOW DISCHARGE
Vitrification
Cryogen name: ETHANE-PROPANE
-
Electron microscopy
Microscope
TFS KRIOS
Image recording
Film or detector model: GATAN K3 BIOCONTINUUM (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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