TY - JOUR
T1 - Structure of the Human FANCL RING-Ube2T Complex Reveals Determinants of Cognate E3-E2 Selection
AU - Hodson, Charlotte
AU - Purkiss, Andrew
AU - Miles, Jennifer Anne
AU - Walden, Helen
N1 - Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2014/2
Y1 - 2014/2
N2 - The combination of an E2 ubiquitin-conjugating enzyme with an E3 ubiquitin-ligase is essential for ubiquitin modification of a substrate. Moreover, the pairing dictates both the substrate choice and the modification type. The molecular details of generic E3-E2 interactions are well established. Nevertheless, the determinants of selective, specific E3-E2 recognition are not understood. There are ~40 E2s and ~600 E3s giving rise to a possible ~24,000 E3-E2 pairs. Using the Fanconi Anemia pathway exclusive E3-E2 pair, FANCL-Ube2T, we report the atomic structure of the FANCL RING-Ube2T complex, revealing a specific and extensive network of additional electrostatic and hydrophobic interactions. Furthermore, we show that these specific interactions are required for selection of Ube2T over other E2s by FANCL.
AB - The combination of an E2 ubiquitin-conjugating enzyme with an E3 ubiquitin-ligase is essential for ubiquitin modification of a substrate. Moreover, the pairing dictates both the substrate choice and the modification type. The molecular details of generic E3-E2 interactions are well established. Nevertheless, the determinants of selective, specific E3-E2 recognition are not understood. There are ~40 E2s and ~600 E3s giving rise to a possible ~24,000 E3-E2 pairs. Using the Fanconi Anemia pathway exclusive E3-E2 pair, FANCL-Ube2T, we report the atomic structure of the FANCL RING-Ube2T complex, revealing a specific and extensive network of additional electrostatic and hydrophobic interactions. Furthermore, we show that these specific interactions are required for selection of Ube2T over other E2s by FANCL.
U2 - 10.1016/j.str.2013.12.004
DO - 10.1016/j.str.2013.12.004
M3 - Article
C2 - 24389026
SN - 0969-2126
VL - 22
SP - 337
EP - 344
JO - Structure
JF - Structure
IS - 2
ER -