Structural Studies of HHARI/UbcH7∼Ub Reveal Unique E2∼Ub Conformational Restriction by RBR RING1.

Publication Type:

Journal Article


Structure, Volume 25, Issue 6, p.890-900.e5 (2017)


<p>RING-between-RING (RBR) E3s contain RING1 domains that are structurally similar yet mechanistically distinct from canonical RING domains. Both types of E3 bind E2&sim;ubiquitin (E2&sim;Ub) via their RINGs but canonical RING E3s promote closed E2&sim;Ub conformations required for direct Ub transfer from the E2 to substrate, while RBR RING1s promote open E2&sim;Ub to favor Ub transfer to the E3 active site. This different RING/E2&sim;Ub conformation determines its direct target, which for canonical RING E3s is typically a substrate or substrate-linked Ub, but is the E3&nbsp;active-site cysteine in the case of RBR-type E3s. Here we show that a short extension of HHARI RING1, namely Zn(2+)-loop II, not present in any RING E3s, acts as a steric wedge to disrupt closed E2&sim;Ub, providing a structural explanation for the distinctive RING1-dependent conformational restriction mechanism utilized by RBR E3s.</p>