The molecular basis for histone H4- and H2A-specific amino-terminal acetylation by NatD

Structure
Robert S MaginRonen Marmorstein

Abstract

N-terminal acetylation is among the most common protein modifications in eukaryotes and is mediated by evolutionarily conserved N-terminal acetyltransferases (NATs). NatD is among the most selective NATs; its only known substrates are histones H4 and H2A, containing the N-terminal sequence SGRGK in humans. Here we characterize the molecular basis for substrate-specific acetylation by NatD by reporting its crystal structure bound to cognate substrates and performing related biochemical studies. A novel N-terminal segment wraps around the catalytic core domain to make stabilizing interactions, and the α1-α2 and β6-β7 loops adopt novel conformations to properly orient the histone N termini in the binding site. Ser1 and Arg3 of the histone make extensive contacts to highly conserved NatD residues in the substrate binding pocket, and flanking glycine residues also appear to contribute to substrate-specific binding by NatD, together defining a Ser-Gly-Arg-Gly recognition sequence. These studies have implications for understanding substrate-specific acetylation by NAT enzymes.

References

Jan 1, 2003·Journal of Molecular Biology·Bogdan Polevoda, Fred Sherman
Dec 8, 2004·Archives of Biochemistry and Biophysics·Matthew W VettingJohn S Blanchard
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jan 30, 2010·Science·Cheol-Sang HwangAlexander Varshavsky
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Jun 10, 2011·PLoS Biology·Gabriella M A ForteColin J Stirling
Aug 9, 2011·Methods : a Companion to Methods in Enzymology·Paul D AdamsPeter H Zwart
Mar 7, 2012·Oncogene·T V Kalvik, Thomas Arnesen
Mar 13, 2012·Trends in Biochemical Sciences·Kristian K StarheimThomas Arnesen
Jul 21, 2012·Proceedings of the National Academy of Sciences of the United States of America·Petra Van DammeRafael Aldabe
Nov 24, 2012·Biopolymers·Hua Yuan, Ronen Marmorstein
Aug 6, 2013·Nature Structural & Molecular Biology·Glen LiszczakRonen Marmorstein
Aug 13, 2013·Nature Structural & Molecular Biology·Nadia ArnaudoFabrizio Martino
Aug 21, 2013·Proceedings of the National Academy of Sciences of the United States of America·Glen Liszczak, Ronen Marmorstein
Nov 20, 2013·Journal of Molecular Modeling·Roch Paweł Jędrzejewski, Rajmund Kaźmierkiewicz

Citations

Dec 17, 2015·Apoptosis : an International Journal on Programmed Cell Death·Demetria Pavlou, Antonis Kirmizis
Aug 9, 2016·Trends in Biochemical Sciences·Henriette AksnesThomas Arnesen
Aug 8, 2018·Cytoskeleton·Thomas ArnesenRoberto Dominguez
Mar 28, 2018·Proceedings of the National Academy of Sciences of the United States of America·Marianne GorisThomas Arnesen
Jul 29, 2018·Experimental & Molecular Medicine·Yiyang Wu, Gholson J Lyon
Feb 12, 2020·Nature Communications·Sunbin DengRonen Marmorstein
Jan 13, 2016·The Journal of Biological Chemistry·Robert S MaginRonen Marmorstein
Jul 19, 2020·Epigenetics & Chromatin·Christina DemetriadouAntonis Kirmizis
Jul 29, 2018·Experimental & Molecular Medicine·Rasmus ReeThomas Arnesen
Apr 3, 2019·Nature Structural & Molecular Biology·Liyong DongZhiwei Huang
Mar 13, 2019·Cell Death & Disease·Christina DemetriadouAntonis Kirmizis
Sep 27, 2020·The Journal of Biological Chemistry·Rasmus ReeThomas Arnesen
Dec 29, 2020·PLoS Computational Biology·Bojan KrtenicNathalie Reuter
Mar 25, 2020·Computational and Structural Biotechnology Journal·Angèle AbboudNathalie Reuter
Jan 14, 2021·International Journal of Molecular Sciences·Yi-Hsun HoRong Huang
Jan 18, 2021·The Journal of Biological Chemistry·Rasmus ReeThomas Arnesen
May 1, 2021·International Journal of Molecular Sciences·Veronique Jonckheere, Petra Van Damme
May 22, 2021·Structure·Sunbin DengRonen Marmorstein
Jun 11, 2021·Journal of Medicinal Chemistry·Youchao DengRong Huang

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