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Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase

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...

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Autores principales: Chen, Ji-Yun, Liu, Liang, Cao, Chun-Ling, Li, Mei-Jun, Tan, Kemin, Yang, Xiaohan, Yun, Cai-Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993997/
https://www.ncbi.nlm.nih.gov/pubmed/27550639
http://dx.doi.org/10.1038/srep31425
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author Chen, Ji-Yun
Liu, Liang
Cao, Chun-Ling
Li, Mei-Jun
Tan, Kemin
Yang, Xiaohan
Yun, Cai-Hong
author_facet Chen, Ji-Yun
Liu, Liang
Cao, Chun-Ling
Li, Mei-Jun
Tan, Kemin
Yang, Xiaohan
Yun, Cai-Hong
author_sort Chen, Ji-Yun
collection PubMed
description 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.
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spelling pubmed-49939972016-08-30 Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase Chen, Ji-Yun Liu, Liang Cao, Chun-Ling Li, Mei-Jun Tan, Kemin Yang, Xiaohan Yun, Cai-Hong Sci Rep Article 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. Nature Publishing Group 2016-08-23 /pmc/articles/PMC4993997/ /pubmed/27550639 http://dx.doi.org/10.1038/srep31425 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Chen, Ji-Yun
Liu, Liang
Cao, Chun-Ling
Li, Mei-Jun
Tan, Kemin
Yang, Xiaohan
Yun, Cai-Hong
Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase
title Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase
title_full Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase
title_fullStr Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase
title_full_unstemmed Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase
title_short Structure and function of human Naa60 (NatF), a Golgi-localized bi-functional acetyltransferase
title_sort structure and function of human naa60 (natf), a golgi-localized bi-functional acetyltransferase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993997/
https://www.ncbi.nlm.nih.gov/pubmed/27550639
http://dx.doi.org/10.1038/srep31425
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