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 Nε -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:
-
- Peking Univ. Health Science Center, Beijing (China)
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- National Basic Research Program of China; Ministry of Science and Technology of the People's Republic of China; National Science Foundation of China; USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1336818
- Grant/Contract Number:
- AC02-06CH11357
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Scientific Reports
- Additional Journal Information:
- Journal Volume: 6
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES
Citation Formats
Chen, Ji-Yun, Liu, Liang, Cao, Chun-Ling, Li, Mei-Jun, Tan, Kemin, Yang, Xiaohan, and Yun, Caihong. Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase. United States: N. p., 2016.
Web. doi:10.1038/srep31425.
Chen, Ji-Yun, Liu, Liang, Cao, Chun-Ling, Li, Mei-Jun, Tan, Kemin, Yang, Xiaohan, & Yun, Caihong. Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase. United States. https://doi.org/10.1038/srep31425
Chen, Ji-Yun, Liu, Liang, Cao, Chun-Ling, Li, Mei-Jun, Tan, Kemin, Yang, Xiaohan, and Yun, Caihong. Tue .
"Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase". United States. https://doi.org/10.1038/srep31425. https://www.osti.gov/servlets/purl/1336818.
@article{osti_1336818,
title = {Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase},
author = {Chen, Ji-Yun and Liu, Liang and Cao, Chun-Ling and Li, Mei-Jun and Tan, Kemin and Yang, Xiaohan and Yun, Caihong},
abstractNote = {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 Nε -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.},
doi = {10.1038/srep31425},
journal = {Scientific Reports},
number = ,
volume = 6,
place = {United States},
year = {Tue Aug 23 00:00:00 EDT 2016},
month = {Tue Aug 23 00:00:00 EDT 2016}
}
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Works referencing / citing this record:
Molecular determinants of the N-terminal acetyltransferase Naa60 anchoring to the Golgi membrane
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