title: Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase.
abstract: N-terminal acetylation (Nt-acetylation), carried out by N-terminal acetyltransferases (NATs), is a conserved and primary modification of nascent peptide chains. Naa60 (also named NatF) is a recently identified NAT found only in multicellular eukaryotes. This protein was shown to locate on the Golgi apparatus and mainly catalyze the Nt-acetylation of transmembrane proteins, and it also harbors lysine N(ε)-acetyltransferase (KAT) activity to catalyze the acetylation of lysine ε-amine. Here, we report the crystal structures of human Naa60 (hNaa60) in complex with Acetyl-Coenzyme A (Ac-CoA) or Coenzyme A (CoA). The hNaa60 protein contains an amphipathic helix following its GNAT domain that may contribute to Golgi localization of hNaa60, and the β7-β8 hairpin adopted different conformations in the hNaa60(1-242) and hNaa60(1-199) crystal structures. Remarkably, we found that the side-chain of Phe 34 can influence the position of the coenzyme, indicating a new regulatory mechanism involving enzyme, co-factor and substrates interactions. Moreover, structural comparison and biochemical studies indicated that Tyr 97 and His 138 are key residues for catalytic reaction and that a non-conserved β3-β4 long loop participates in the regulation of hNaa60 activity.
authors.affiliation: Department of Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, P. R. China.|Institute of Systems Biomedicine and Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, P. R. China.
authors.forename: Ji-Yun
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Department of Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, P. R. China.|Institute of Systems Biomedicine and Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, P. R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, P. R. China.|Institute of Systems Biomedicine and Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, P. R. China.
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Cao
authors.affiliation: Department of Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, P. R. China.
authors.forename: Mei-Jun
authors.initials: MJ
authors.lastname: Li
authors.affiliation: Structural Biology Center, Biosciences, Argonne National Laboratory, 9700 S. Cass Avenue, Argonne, IL 60439, USA.
authors.forename: Kemin
authors.initials: K
authors.lastname: Tan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Biophysics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, P. R. China.|Institute of Systems Biomedicine and Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, P. R. China.
authors.forename: Cai-Hong
authors.initials: CH
authors.lastname: Yun
mesh_terms: D000105:Acetyl Coenzyme A / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000107:Acetylation; D006056:Golgi Apparatus / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D063214:N-Terminal Acetyltransferase F / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
chemical_list: C570958:NAA60 protein, human; D000105:Acetyl Coenzyme A; D063214:N-Terminal Acetyltransferase F; D008239:Lysine