Mechanistic basis for the role of acidic tail of Rad6 (ubiquitin-conjugating enzyme) in Bre1 (E3 ligase) mediated recognition of histones in Saccharomyces cerevisiae

E2 Rad6 and E3 Bre1 are indispensable for H2B K123 monoubiquitination in budding yeast however, the mechanistic basis for the fidelity of the ubiquitination reaction was not clear.The present study reveals two important findings: (i) ) the involvement of Rad6 acidic tail and a positive charged surface of histone H2B in E2-NCP recognition prior to ubiquitin transfer, and (ii) direct interaction of Bre1 RBD with Rad6 prevents promiscuous ubiquitin transfer to histone lysine residues, allowing site-specific monoubiquitination in conjunction with the RING domain ConclusionResults