skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Journal Article · · Scientific Reports
DOI:https://doi.org/10.1038/srep31425· OSTI ID:1336818
 [1];  [1];  [1];  [1];  [2];  [1];  [1]
  1. Peking Univ. Health Science Center, Beijing (China)
  2. Argonne National Lab. (ANL), Argonne, IL (United States)
+ Show Author Affiliations

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
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)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1336818
Journal Information:
Scientific Reports, Vol. 6
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 25 works
Citation information provided by
Web of Science

References (40)

NatF Contributes to an Evolutionary Shift in Protein N-Terminal Acetylation and Is Important for Normal Chromosome Segregation journal July 2011
PHENIX: a comprehensive Python-based system for macromolecular structure solution. text January 2010
Emerging Functions for N-Terminal Protein Acetylation in Plants journal October 2015
Amphipathic helices and membrane curvature journal October 2009
N-terminal modifications of cellular proteins: The enzymes involved, their substrate specificities and biological effects journal June 2015
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination journal September 1998
Regulation of the p300 HAT domain via a novel activation loop journal March 2004
Molecular basis for N-terminal acetylation by the heterodimeric NatA complex journal August 2013
Protein N-terminal acetyltransferases: when the start matters journal April 2012
Protein N-terminal acetyltransferases in cancer journal March 2012
Developmental roles of protein N-terminal acetylation journal June 2015
Scaling and assessment of data quality journal December 2005
An Organellar Nα-Acetyltransferase, Naa60, Acetylates Cytosolic N Termini of Transmembrane Proteins and Maintains Golgi Integrity journal March 2015
Implications for the evolution of eukaryotic amino-terminal acetyltransferase (NAT) enzymes from the structure of an archaeal ortholog journal August 2013
The Influenza A Virus PB1-F2 Protein Targets the Inner Mitochondrial Membrane via a Predicted Basic Amphipathic Helix That Disrupts Mitochondrial Function journal July 2003
N-Terminal Acetylation of Cellular Proteins Creates Specific Degradation Signals journal January 2010
GCN5-Related N-Acetyltransferases: A Structural Overview journal June 2000
Histone acetyltransferase complexes: one size doesn't fit all journal April 2007
Hat2p recognizes the histone H3 tail to specify the acetylation of the newly synthesized H3/H4 heterodimer by the Hat1p/Hat2p complex journal May 2014
Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. journal January 1993
HAT4, a Golgi Apparatus-Anchored B-Type Histone Acetyltransferase, Acetylates Free Histone H4 and Facilitates Chromatin Assembly journal October 2011
Tetrahymena Histone Acetyltransferase A: A Homolog to Yeast Gcn5p Linking Histone Acetylation to Gene Activation journal March 1996
HKL -3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes journal July 2006
Structure and ligand of a histone acetyltransferase bromodomain journal June 1999
Coot model-building tools for molecular graphics journal November 2004
An N-terminal Amphipathic Helix Binds Phosphoinositides and Enhances Kalirin Sec14 Domain-mediated Membrane Interactions journal April 2015
Structure of Tetrahymena GCN5 bound to coenzyme A and a histone H3 peptide journal September 1999
The biological functions of Naa10 – from amino-terminal acetylation to human disease posted_content April 2015
Application of a Fluorescent Histone Acetyltransferase Assay to Probe the Substrate Specificity of the Human p300/CBP-Associated Factor journal December 2000
Structure of a Ternary Naa50p (NAT5/SAN) N-terminal Acetyltransferase Complex Reveals the Molecular Basis for Substrate-specific Acetylation journal September 2011
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
The Molecular Basis for Histone H4- and H2A-Specific Amino-Terminal Acetylation by NatD journal February 2015
The biological functions of Naa10 — From amino-terminal acetylation to human disease journal August 2015
Melatonin Production: Proteasomal Proteolysis in Serotonin N-Acetyltransferase Regulation journal February 1998
Lipidation of the LC3/GABARAP family of autophagy proteins relies on a membrane-curvature-sensing domain in Atg3 journal April 2014
PRODRG, a program for generating molecular topologies and unique molecular descriptors from coordinates of small molecules journal June 1996
Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes journal March 1993
Human Naa50p (Nat5/San) Displays Both Protein N α - and N ϵ -Acetyltransferase Activity journal September 2009
Phaser crystallographic software journal July 2007
Proteome-derived Peptide Libraries Allow Detailed Analysis of the Substrate Specificities of N α -acetyltransferases and Point to hNaa10p as the Post-translational Actin N α -acetyltransferase journal March 2011

Cited By (1)

Molecular determinants of the N-terminal acetyltransferase Naa60 anchoring to the Golgi membrane journal February 2017

Similar Records

Related Subjects

60 APPLIED LIFE SCIENCES