| Structural highlights
Function
NAA38_HUMAN Auxillary component of the N-terminal acetyltransferase C (NatC) complex which catalyzes acetylation of N-terminal methionine residues (PubMed:19398576, PubMed:37891180). N-terminal acetylation protects proteins from ubiquitination and degradation by the N-end rule pathway (PubMed:37891180).[1] [2]
Publication Abstract from PubMed
N-terminal acetylation occurs on over 80% of human proteins and is catalyzed by a family of N-terminal acetyltransferases (NATs). All NATs contain a small catalytic subunit, while some also contain a large auxiliary subunit that facilitates catalysis and ribosome targeting for co-translational acetylation. NatC is one of the major NATs containing an NAA30 catalytic subunit, but uniquely contains two auxiliary subunits, large NAA35 and small NAA38. Here, we report the cryo-EM structures of human NatC (hNatC) complexes with and without NAA38, together with biochemical studies, to reveal that NAA38 increases the thermostability and broadens the substrate-specificity profile of NatC by ordering an N-terminal segment of NAA35 and reorienting an NAA30 N-terminal peptide binding loop for optimal catalysis, respectively. We also note important differences in engagement with a stabilizing inositol hexaphosphate molecule between human and yeast NatC. These studies provide new insights for the function and evolution of the NatC complex.
Molecular role of NAA38 in thermostability and catalytic activity of the human NatC N-terminal acetyltransferase.,Deng S, Gardner SM, Gottlieb L, Pan B, Petersson EJ, Marmorstein R Structure. 2023 Feb 2;31(2):166-173.e4. doi: 10.1016/j.str.2022.12.008. Epub 2023 , Jan 12. PMID:36638802[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Starheim KK, Gromyko D, Evjenth R, Ryningen A, Varhaug JE, Lillehaug JR, Arnesen T. Knockdown of human N alpha-terminal acetyltransferase complex C leads to p53-dependent apoptosis and aberrant human Arl8b localization. Mol Cell Biol. 2009 Jul;29(13):3569-81. Epub 2009 Apr 27. PMID:19398576 doi:http://dx.doi.org/MCB.01909-08
- ↑ Varland S, Silva RD, Kjosås I, Faustino A, Bogaert A, Billmann M, Boukhatmi H, Kellen B, Costanzo M, Drazic A, Osberg C, Chan K, Zhang X, Tong AHY, Andreazza S, Lee JJ, Nedyalkova L, Ušaj M, Whitworth AJ, Andrews BJ, Moffat J, Myers CL, Gevaert K, Boone C, Martinho RG, Arnesen T. N-terminal acetylation shields proteins from degradation and promotes age-dependent motility and longevity. Nat Commun. 2023 Oct 27;14(1):6774. PMID:37891180 doi:10.1038/s41467-023-42342-y
- ↑ Deng S, Gardner SM, Gottlieb L, Pan B, Petersson EJ, Marmorstein R. Molecular role of NAA38 in thermostability and catalytic activity of the human NatC N-terminal acetyltransferase. Structure. 2023 Feb 2;31(2):166-173.e4. PMID:36638802 doi:10.1016/j.str.2022.12.008
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