Oligomerization-primed coiled-coil domain interaction with Ubc13 confers processivity to TRAF6 ubiquitin ligase activity

• DOI: 10.1038/s41467-017-01290-0
• Publication Date: 2017-10-04T06:54:03Z
• Authors: Lin Hu; Jiafeng Xu; Xiaomei Xie; Yiwen Zhou; Panfeng Tao; Haidong Li; Xu Han; Chong Wang; Jian Liu; Pinglong Xu; Dante Neculai; Zongping Xia
• Keywords: Processivity; Ubiquitin-conjugating enzyme

Abstract Ubiquitin ligase TRAF6, together with ubiquitin-conjugating enzyme Ubc13/Uev1, catalyzes processive assembly of unanchored K63-linked polyubiquitin chains for TAK1 activation in the IL-1R/TLR pathways. However, what domain and how it functions to enable TRAF6’s processivity are largely uncharacterized. Here, we find TRAF6 coiled-coil (CC) is crucial its processivity. The CC mediates oligomerization ensure efficient long chain assembly. Mutating or deleting impairs Fusion E3 ubiquitin CHIP/STUB1 renders latter capable NF-κB activation. Moreover, domain, after oligomerization, interacts Ubc13/Ub~Ubc13, which further contributes Point mutations within that weaken interaction Ubc13/Ub~Ubc13 diminish Our results reveal primes confer activity.