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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.

SUBMITTER: Hodson C

PROVIDER: S-EPMC3979106 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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

Hodson Charlotte C Purkiss Andrew A Miles Jennifer Anne JA Walden Helen H

Structure (London, England : 1993) 20140102 2

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 e ...[more]

PMID: 24389026

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