N-terminal acetylation is among the most common protein modifications in eukaryotes and is mediated by evolutionarily conserved N-terminal acetyltransferases (NATs). NatD is among the most selective NATs; its only known substrates are histones H4 and H2A, containing the N-terminal sequence SGRGK in humans. Here we characterize the molecular basis for substrate-specific acetylation by NatD by reporting its crystal structure bound to cognate substrates and performing related biochemical studies. A novel N-terminal segment wraps around the catalytic core domain to make stabilizing interactions, and the α1-α2 and β6-β7 loops adopt novel conformations to properly orient the histone N termini in the binding site. Ser1 and Arg3 of the histone make extensive contacts to highly conserved NatD residues in the substrate binding pocket, and flanking glycine residues also appear to contribute to substrate-specific binding by NatD, together defining a Ser-Gly-Arg-Gly recognition sequence. These studies have implications for understanding substrate-specific acetylation by NAT enzymes.
Five SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin (SMARC) genes are dispersed in the human genome
The catalytic mechanism of the ESA1 histone acetyltransferase involves a self-acetylated intermediate
N-terminal acetyltransferases and sequence requirements for N-terminal acetylation of eukaryotic proteins
Patt1, a novel protein acetyltransferase that is highly expressed in liver and downregulated in hepatocellular carcinoma, enhances apoptosis of hepatoma cells
NatF contributes to an evolutionary shift in protein N-terminal acetylation and is important for normal chromosome segregation
Structure of a ternary Naa50p (NAT5/SAN) N-terminal acetyltransferase complex reveals the molecular basis for substrate-specific acetylation.
The human N-alpha-acetyltransferase 40 (hNaa40p/hNatD) is conserved from yeast and N-terminally acetylates histones H2A and H4
Liver Patt1 deficiency protects male mice from age-associated but not high-fat diet-induced hepatic steatosis.
Implications for the evolution of eukaryotic amino-terminal acetyltransferase (NAT) enzymes from the structure of an archaeal ortholog
N-alpha-terminal acetylation of histone H4 regulates arginine methylation and ribosomal DNA silencing
Hat2p recognizes the histone H3 tail to specify the acetylation of the newly synthesized H3/H4 heterodimer by the Hat1p/Hat2p complex
Depletion of histone N-terminal-acetyltransferase Naa40 induces p53-independent apoptosis in colorectal cancer cells via the mitochondrial pathway
N-terminal modifications of cellular proteins: The enzymes involved, their substrate specificities and biological effects
Crystal Structure of the Golgi-Associated Human Nα-Acetyltransferase 60 Reveals the Molecular Determinants for Substrate-Specific Acetylation
NAA10 dysfunction with normal NatA-complex activity in a girl with non-syndromic ID and a de novo NAA10 p.(V111G) variant - a case report
N-terminal acetylation: an essential protein modification emerges as an important regulator of stress responses
Loss of Nat4 and its associated histone H4 N-terminal acetylation mediates calorie restriction-induced longevity
NatD promotes lung cancer progression by preventing histone H4 serine phosphorylation to activate Slug expression
A novel NAA10 p.(R83H) variant with impaired acetyltransferase activity identified in two boys with ID and microcephaly
Structural determinants and cellular environment define processed actin as the sole substrate of the N-terminal acetyltransferase NAA80
A novel NAA10 variant with impaired acetyltransferase activity causes developmental delay, intellectual disability, and hypertrophic cardiomyopathy
Human Naa50 Protein Displays Broad Substrate Specificity for Amino-terminal Acetylation: DETAILED STRUCTURAL AND BIOCHEMICAL ANALYSIS USING TETRAPEPTIDE LIBRARY.
Exploring the Complexity of Protein-Level Dosage Compensation that Fine-Tunes Stoichiometry of Multiprotein Complexes
Divergent architecture of the heterotrimeric NatC complex explains N-terminal acetylation of cognate substrates
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