ArticleProceedings of the National Academy of Sciences of the United States of America2018
Structural determinants and cellular environment define processed actin as the sole substrate of the N-terminal acetyltransferase NAA80.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 76 citations in OpenAlex.
- Histone and N-terminal acetyltransferases play important roles in female reproduction and embryogenesis of the red flour beetle Tribolium castaneum.Insect molecular biology · 2025Article
- Illuminating the impact of N-terminal acetylation: from protein to physiology.Nature communications · 2025Review
- The kinetoplastid kinetochore protein KKT23 acetyltransferase is a structural homolog of GCN5 that acetylates the histone H2A C-terminal tail.Structure (London, England : 1993) · 2025Article
- Naa80 is required for actin N-terminal acetylation and normal hearing in zebrafish.Life science alliance · 2024Article
- Diverging co-translational protein complex assembly pathways are governed by interface energy distribution.Nature communications · 2024Article
- IntAct: A nondisruptive internal tagging strategy to study the organization and function of actin isoforms.PLoS biology · 2024Article
- N-terminal acetyltransferase 6 facilitates enterovirus 71 replication by regulating PI4KB expression and replication organelle biogenesis.Journal of virology · 2024Article
- Purification of modified mammalian actin isoforms for in vitro reconstitution assays.European journal of cell biology · 2023Review
- N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity.Nature communications · 2023Article
- Impact of Protein NLife (Basel, Switzerland) · 2023Review
- Optimized bisubstrate inhibitors for the actin N-terminal acetyltransferase NAA80.Frontiers in chemistry · 2023Article
- NAA60 (HAT4): the newly discovered bi-functional Golgi member of the acetyltransferase family.Clinical epigenetics · 2022Review
- From Nucleus to Membrane: A Subcellular Map of the N-Acetylation Machinery in Plants.International journal of molecular sciences · 2022Review
- Extended N-Terminal Acetyltransferase Naa50 in Filamentous Fungi Adds to Naa50 Diversity.International journal of molecular sciences · 2022Article
- Investigating Peptide-Coenzyme A Conjugates as Chemical Probes for Proteomic Profiling of N-Terminal and Lysine Acetyltransferases.Chembiochem : a European journal of chemical biology · 2022Article
- The Final Maturation State of β-actin Involves N-terminal Acetylation by NAA80, not N-terminal Arginylation by ATE1.Journal of molecular biology · 2022Article
- Hydroxylation of the Acetyltransferase NAA10 Trp38 Is Not an Enzyme-Switch in Human Cells.International journal of molecular sciences · 2021Article
- Molecular mechanism of N-terminal acetylation by the ternary NatC complex.Structure (London, England : 1993) · 2021Article
- Novel Bisubstrate Inhibitors for Protein N-Terminal Acetyltransferase D.Journal of medicinal chemistry · 2021Article
- Posttranslational modifications of the cytoskeleton.Cytoskeleton (Hoboken, N.J.) · 2021Review
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13 authors at 3 institutions in 2 countries.
Funding
Abstract
N-terminal (Nt) acetylation is a major protein modification catalyzed by N-terminal acetyltransferases (NATs). Methionine acidic N termini, including actin, are cotranslationally Nt acetylated by NatB in all eukaryotes, but animal actins containing acidic N termini, are additionally posttranslationally Nt acetylated by NAA80. Actin Nt acetylation was found to regulate cytoskeletal dynamics and motility, thus making NAA80 a potential target for cell migration regulation. In this work, we developed potent and selective bisubstrate inhibitors for NAA80 and determined the crystal structure of NAA80 in complex with such an inhibitor, revealing that NAA80 adopts a fold similar to other NAT enzymes but with a more open substrate binding region. Furthermore, in contrast to most other NATs, the substrate specificity of NAA80 is mainly derived through interactions between the enzyme and the acidic amino acids at positions 2 and 3 of the actin substrate and not residues 1 and 2. A yeast model revealed that ectopic expression of NAA80 in a strain lacking NatB activity partially restored Nt acetylation of NatB substrates, including yeast actin. Thus, NAA80 holds intrinsic capacity to posttranslationally Nt acetylate NatB-type substrates in vivo. In sum, the presence of a dominant cotranslational NatB in all eukaryotes, the specific posttranslational actin methionine removal in animals, and finally, the unique structural features of NAA80 leave only the processed actins as in vivo substrates of NAA80. Together, this study reveals the molecular and cellular basis of NAA80 Nt acetylation and provides a scaffold for development of inhibitors for the regulation of cytoskeletal properties.
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