The research groups led by Professor Koichi Kato of the Institutes for Molecular Science and the Okazaki Institutes for Integrative Bioscience have provided structural basis for the mechanisms underlying the conjugation of ubiquitin (Ub) to proteins as targets for proteasomal degradation.
The formation and elongation of the polyubiquitin chain are carried out through a cascade of E1, E2 and E3 enzymes. E2 ubiquitin-conjugating enzymes catalyze the attachment of Ub to the lysine residues of target proteins captured by E3. A key question in ubiquitination is how E2-E3 complex can deal with the various acceptor sites distributed on the substrate surface.
The research groups focused on UbcH5b, one of E2 enzymes that has been demonstrated to collaborate with several E3 enzymes, and determined the three-dimensional structure of an intermediate of the E2~ubiquitin conjugate by combined use of X-ray crystallography [in collaboration with Professor Soichi Wakatsuki of High Energy Accelerator Research Organization (KEK)] and NMR spectroscopy. Interestingly, the E2~ubiquitin conjugate is assembled into an infinite spiral through the non-covalent backside interaction. These findings, along with their biochemical data, underline the significance of a “riding-on” mechanism, in which the self-assembled E2~Ub conjugates serve as a bridge between the E3 and the acceptor sites, as one of the molecular strategies employed for efficient and versatile ubiquitination of substrates.
The riding-on mechanism of ubiquitin conjugation: the E2 conjugated to Ub is assembled into a spiral structure and thereby bridges the gap between the E3 and the acceptor sites.
Paper Information
Jornal:Structure, vol.18，137 - 147 (January 13, 2010)
Title: Crystal structure of UbcH5b~ubiquitin intermediate: Insight into the formation of the self-assembled E2~Ub conjugates
Author: Eri Sakata, Tadashi Satoh, Shunsuke Yamamoto, Yoshiki Yamaguchi, Maho Yagi-Utsumi, Eiji Kurimoto, Keiji Tanaka, Soichi Wakatsuki, Koichi Kato
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