Structural insights into the mechanism and E2 specificity of the RBR E3 ubiquitin ligase HHARI

Lingmin Yuan; Zongyang Lv; James H. Atkison; Shaun K. Olsen

doi:10.1038/s41467-017-00272-6

journal article Open Access Aug 08, 2017

Structural insights into the mechanism and E2 specificity of the RBR E3 ubiquitin ligase HHARI

Lingmin Yuan Zongyang Lv James H. Atkison Shaun K. Olsen

Nature Communications Vol. 8 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/s41467-017-00272-6

Abstract

AbstractRING-in-between-RING (RBR) ubiquitin (Ub) E3 ligases function with Ub E2s through a RING/HECT hybrid mechanism to conjugate Ub to target proteins. Here, we report the crystal structure of the RBR E3, HHARI, in complex with a UbcH7 ~ Ub thioester mimetic which reveals the molecular basis for the specificity of this cognate E2/RBR E3 pair. The structure also reveals mechanistically important conformational changes in the RING1 and UBA-like domains of HHARI that accompany UbcH7 ~ Ub binding and provides a molecular basis by which HHARI recruits E2 ~ Ub in an ‘open’ conformation. In addition to optimally functioning with an E2 that solely performs transthiolation, our data suggests that HHARI prevents spurious discharge of Ub from E2 to lysine residues by: (1) harboring structural elements that block E2 ~ Ub from adopting a ‘closed’ conformation and (2) participating in contacts to ubiquitin that promote an open E2 ~ Ub conformation.

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Published: Aug 08, 2017
Vol/Issue: 8(1)
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Cite This Article

Lingmin Yuan, Zongyang Lv, James H. Atkison, et al. (2017). Structural insights into the mechanism and E2 specificity of the RBR E3 ubiquitin ligase HHARI. Nature Communications, 8(1). https://doi.org/10.1038/s41467-017-00272-6

Structural insights into the mechanism and E2 specificity of the RBR E3 ubiquitin ligase HHARI

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