Structurally distinct ubiquitin- and sumo-modified PCNA: implications for their distinct roles in the DNA damage response

Structure
Susan E TsutakawaIvaylo Ivanov

Abstract

Proliferating cell nuclear antigen (PCNA) is a pivotal replication protein, which also controls cellular responses to DNA damage. Posttranslational modification of PCNA by SUMO and ubiquitin modulate these responses. How the modifiers alter PCNA-dependent DNA repair and damage tolerance pathways is largely unknown. We used hybrid methods to identify atomic models of PCNAK107-Ub and PCNAK164-SUMO consistent with small-angle X-ray scattering data of these complexes in solution. We show that SUMO and ubiquitin have distinct modes of association to PCNA. Ubiquitin adopts discrete docked binding positions. By contrast, SUMO associates by simple tethering and adopts extended flexible conformations. These structural differences are the result of the opposite electrostatic potentials of SUMO and Ub. The unexpected contrast in conformational behavior of Ub-PCNA and SUMO-PCNA has implications for interactions with partner proteins, interacting surfaces accessibility, and access points for pathway regulation.

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Citations

Nov 12, 2015·Computational and Structural Biotechnology Journal·Xiaojun XuIvaylo Ivanov
Jun 21, 2015·Current Opinion in Chemical Biology·Grace H Pham, Eric R Strieter
Sep 24, 2015·Journal of Molecular Biology·Joseph S HarrisonBrian Kuhlman
Oct 28, 2015·Scientific Reports·Wilson C Y LauMichael S Y Huen
Oct 13, 2017·Open Biology·Yanfang YangShufang Liang
Sep 5, 2019·Acta Neuropathologica Communications·Lisa MaPaul J Hagerman
Jun 3, 2016·PLoS Computational Biology·K Aurelia BallMatthew P Jacobson
Dec 21, 2016·Nucleic Acids Research·Aishwarya PrakashSylvie Doublié
Jun 4, 2018·Nucleic Acids Research·Dina DaitchmanYaakov Levy
Dec 28, 2018·Genes·Wendy LeungAnja-Katrin Bielinsky
Nov 16, 2019·Advanced Theory and Simulations·Christopher MaffeoAleksei Aksimentiev
Feb 6, 2017·Molecular Cell·Katherine N Choe, George-Lucian Moldovan
Nov 2, 2018·Journal of Molecular Biology·Kyle T PowersM Todd Washington
Mar 24, 2020·Journal of Chemical Information and Modeling·Thomas DoddIvaylo Ivanov

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