title: Structure of the human FANCL RING-Ube2T complex reveals determinants of cognate E3-E2 selection.
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.
authors.affiliation: 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.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Hodson
authors.affiliation: 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.
authors.forename: Andrew
authors.initials: A
authors.lastname: Purkiss
authors.affiliation: 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.
authors.forename: Jennifer Anne
authors.initials: JA
authors.lastname: Miles
authors.affiliation: 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.
authors.forename: Helen
authors.initials: H
authors.lastname: Walden
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004260:DNA Repair; D052240:Fanconi Anemia Complementation Group L Protein / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D025801:Ubiquitin / Q000737:chemistry; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry; D014982:Xenopus laevis
chemical_list: D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes; C499908:FANCL protein, human; D052240:Fanconi Anemia Complementation Group L Protein; D044767:Ubiquitin-Protein Ligases