5icv | pdb_00005icv
Crystal structure of human NatF (hNaa60) bound to a bisubstrate analogue
Structural highlights
Function[NAA60_HUMAN] Histone acetyltransferase localized in the Golgi apparatus that mediates acetylation of free histone H4, thereby facilitating nucleosome assembly. Has a preference for free histone H4 'Lys-20'(H4K20ac), 'Lys-79'(H4K79ac) and 'Lys-91' (H4K91ac). Also displays alpha (N-terminal) acetyltransferase activity towards a range of N-terminal sequences including those starting with Met-Lys, Met-Val, Met-Ala and Met-Met. Required for normal chromosomal segregation during anaphase.[1] [2] Publication Abstract from PubMedN-Terminal acetylation is a common and important protein modification catalyzed by N-terminal acetyltransferases (NATs). Six human NATs (NatA-NatF) contain one catalytic subunit each, Naa10 to Naa60, respectively. In contrast to the ribosome-associated NatA to NatE, NatF/Naa60 specifically associates with Golgi membranes and acetylates transmembrane proteins. To gain insight into the molecular basis for the function of Naa60, we developed an Naa60 bisubstrate CoA-peptide conjugate inhibitor, determined its X-ray structure when bound to CoA and inhibitor, and carried out biochemical experiments. We show that Naa60 adapts an overall fold similar to that of the catalytic subunits of ribosome-associated NATs, but with the addition of two novel elongated loops that play important roles in substrate-specific binding. One of these loops mediates a dimer to monomer transition upon substrate-specific binding. Naa60 employs a catalytic mechanism most similar to Naa50. Collectively, these data reveal the molecular basis for Naa60-specific acetyltransferase activity with implications for its Golgi-specific functions. Crystal Structure of the Golgi-Associated Human Nalpha-Acetyltransferase 60 Reveals the Molecular Determinants for Substrate-Specific Acetylation.,Stove SI, Magin RS, Foyn H, Haug BE, Marmorstein R, Arnesen T Structure. 2016 Jul 6;24(7):1044-56. doi: 10.1016/j.str.2016.04.020. Epub 2016, Jun 16. PMID:27320834[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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