Work

Mechanism of ubiquitin transfer promoted by TRAF6

Year: 2018

Type: article

Abstract: Significance Polyubiquitination is critically important for many cellular functions from protein degradation to signal transduction. TNF receptor-associated factor 6 (TRAF6) is a RING-type ubiquitin ligase that promotes polyubiquitination required for the signaling of many innate immune receptors. How TRAF6 uses its RING dimer to facilitate polyubiquitination remains elusive. In this paper, we mapped TRAF6 residues on both subunits of the TRAF6 dimer that are required for this process via allosteric activation. We found that in addition to the RING domain itself, residues outside the RING domain play indispensable roles. Moreover, our studies reveal common features for the activation of polyubiquitination by the RING family and related domains, which shed light on the functional mechanisms of both dimeric and monomeric ubiquitin ligases.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1721788115

Authors: Tian-Min Fu, Chen Shen, Qiubai Li, Pengfei Zhang, Hao Wu

Institutions: Boston Children's Hospital, Harvard University

Language: English

Topic: Ubiquitin and proteasome pathways

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development

Awards: Structural & Functional Studies of TLR/IL-1R Signaling, G1067796009, SMOCs: Novel Signal Transduction Complexes as New Targets for Drug Discovery, Structural & Functional Studies of TLR/IL-1R Signaling