Chemoenzymatic and synthetic approaches to investigate aspartate- and glutamate-ADP-ribosylation

Author(s):
Tashiro, K.; Wijngaarden, S. (0000-0002-6449-4113); Mohapatra, J.; Rack, J.G.M.; Ahel, I.; Filippov, D.V. (0000-0002-6978-7425); Liszczak, G.
Published
2023
Publication type
Article / Letter to editor

Abstract

We report here chemoenzymatic and fully synthetic methodologiesto modify aspartate and glutamate side chains with ADP-ribose at specificsites on peptides. Structural analysis of aspartate and glutamateADP-ribosylated peptides reveals near-quantitative migration of theside chain linkage from the anomeric carbon to the 2 ''- or 3 ''-ADP-ribosehydroxyl moieties. We find that this linkage migration pattern isunique to aspartate and glutamate ADP-ribosylation and propose thatthe observed isomer distribution profile is present in biochemicaland cellular environments. After defining distinct stability propertiesof aspartate and glutamate ADP-ribosylation, we devise methods toinstall homogenous ADP-ribose chains at specific glutamate sites andassemble glutamate-modified peptides into full-length proteins. Byimplementing these technologies, we show that histone H2B E2 tri-ADP-ribosylationis able to stimulate the chromatin remodeler ALC1 with similar efficiencyto histone serine ADP-ribosylation. Our work reveals fundamental principlesof aspartate and glutamate ADP-ribosylation and enables new strategiesto interrogate the biochemical consequences of this widespread proteinmodification.

Date issued
2023-06-14
Language
English
Publisher
AMER CHEMICAL SOC
Is part of
Journal of the American Chemical Society (2023), Vol. 145, no. 25, p. 14000-14009
hdl
1887/3656608
doi
10.1021/jacs.3c03771
URL
https://pubs.acs.org/doi/10.1021/jacs.3c03771