2. Academic Validation
  3. Structure of the human FANCL RING-Ube2T complex reveals determinants of cognate E3-E2 selection

Structure of the human FANCL RING-Ube2T complex reveals determinants of cognate E3-E2 selection

  • Structure. 2014 Feb 4;22(2):337-44. doi: 10.1016/j.str.2013.12.004.
Charlotte Hodson 1,  Andrew Purkiss 1,  Jennifer Anne Miles 1,  Helen Walden 2
Affiliations

Affiliations

  • 1 Protein Structure and Function Laboratory, Lincoln's Inn Fields Laboratories of the London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
  • 2 Protein Structure and Function Laboratory, Lincoln's Inn Fields Laboratories of the London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3LY, UK; MRC-Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, Dow Street, Dundee DD1 5EH, UK. Electronic address: h.walden@dundee.ac.uk.
PMID: 24389026 DOI: 10.1016/j.str.2013.12.004
Abstract

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.

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