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NatB

NatB is an enzyme in an enzyme group called N-terminal acetyltransferases (NATs), which modify proteins by doing N-terminal acetylation. NatB is one of the major NATs in the cell and is a heterodimeric complex found in the cytosol consisting of the auxiliary subunit NAA25, and the catalytic subunit NAA20.[1][2] Subunit NAA25 anchors to the ribosome, and subunit NAA20 is the enzymatic subunit. The NatB complex adds an acetyl group directly on a substrate protein as it is being made on the ribosome, also known as co-translational modification. Studying the NatB complex binding to the ribosome in yeast has shown that NatB is localized at the exit tunnel of the ribosome, and binding of the NatB subunits on the ribosome depends on ES27a (small ribosomal subunit protein).[3] NatB is structurally and biologically the same between yeast (Saccharomyces cerevisiae) and humans.[2]

The structure of the NatB complex in yeast (Candida albicans) was studied in 2017.,[4] and NAA25 seems to create a pocket for NAA20, where target protein is bound to. The NAA20 structure in the thermophilic fungus Chaetomium thermophilum was successfully characterized in 2020,[5] and NAA20 was found to be able to acetylate target proteins in the absence of NAA25, though with a lower acetylation rate than the NAA20/NAA25 complex of NatB.[5] However, NAA20 in humans is unstable in the absence of NAA25 and therefore NatB forms a complex in vivo[2]

NatB is responsible for N-terminally acetylating approximately 20 % of the human proteome.[6] NatB acetylates N-terminal proteins starting with methionine (iMet) followed by


or amidic amino acids, making the target pool to be MD, ME, MN and MQ. Almost 100 % of all the proteins that are target substrates of NatB are N-terminally acetylated, which is a unique feature of NatB compared to other NATs.[6][7] Finding substrates and proteins that are N-terminally acetylated by NatB has been studied in yeast and humans in order to understand the biological function of NatB. In yeast, lack of N-terminal acetylation activity by NatB has an effect on actin and tropomyosin interactions.[1][8] The NF-κB subunit p65 has also been proposed to be a target protein in humans,[2] as well as tropomyosin 1.[7] NatB also seems to potentially regulate the Set-COMPASS subunit protein Swd1 by N-terminal acetylation, and therefore NatB could regulate H3K4 methylation together with NatA.[9] NatB might also regulate NAD+ metabolism in yeast, where knockout of nat3Δ (NAA25) and mdm20Δ (NAA20) decreased the levels of the nicotinamide mononucleotide adenylyltransferase (Nmnat) proteins Nma1 and Nma2[10].

NATs belongs to the GCN5 related N-acetyltransferases (GNAT) superfamily. N-terminal acetylation is the process of adding an acetyl group during or after protein synthesis.[11]

  1. ^ a b Polevoda, B., et al., Nat3p and Mdm20p Are Required for Function of Yeast NatB Nα-terminal Acetyltransferase and of Actin and Tropomyosin*. Journal of Biological Chemistry, 2003. 278(33): p. 30686-30697.
  2. ^ a b c d Starheim, K.K., et al., Identification of the human N(alpha)-acetyltransferase complex B (hNatB): a complex important for cell-cycle progression. Biochem J, 2008. 415(2): p. 325-31.
  3. ^ Knorr, A.G., et al., The dynamic architecture of Map1- and NatB-ribosome complexes coordinates the sequential modifications of nascent polypeptide chains. PLoS Biol, 2023. 21(4): p. e3001995.
  4. ^ Hong, H., et al., Molecular Basis of Substrate Specific Acetylation by N-Terminal Acetyltransferase NatB. Structure, 2017. 25(4): p. 641-649.e3.
  5. ^ a b Layer, D., et al., Structural basis of Naa20 activity towards a canonical NatB substrate. Commun Biol, 2021. 4(1): p. 2.
  6. ^ a b Aksnes, H., N. McTiernan, and T. Arnesen, NATs at a glance. J Cell Sci, 2023. 136(14).
  7. ^ a b Van Damme, P., et al., N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proceedings of the National Academy of Sciences, 2012. 109(31): p. 12449-12454.
  8. ^ Singer, J.M. and J.M. Shaw, Mdm20 protein functions with Nat3 protein to acetylate Tpm1 protein and regulate tropomyosin-actin interactions in budding yeast. Proc Natl Acad Sci U S A, 2003. 100(13): p. 7644-9.
  9. ^ Woo, H., et al., N-terminal acetylation of Set1-COMPASS fine-tunes H3K4 methylation patterns. Sci Adv, 2024. 10(28): p. eadl6280.
  10. ^ Croft, T., et al., N-terminal protein acetylation by NatB modulates the levels of Nmnats, the NAD+ biosynthetic enzymes in Saccharomyces cerevisiae. Journal of Biological Chemistry, 2020. 295(21): p. 7362-7375.
  11. ^ Deng, S. and R. Marmorstein, Protein N-Terminal Acetylation: Structural Basis, Mechanism, Versatility, and Regulation. Trends in Biochemical Sciences, 2020.

NatB

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