LAUSR

For many inflammatory cytokines, the response elicited is dependent on the recruitment of the tumour necrosis factor receptor‐associated factor (TRAF) family of adaptor proteins. All TRAF proteins have a trimeric C‐terminal TRAF domain, while at the N‐terminus most TRAFs have a RING domain that forms dimers. The symmetry mismatch of the N‐ and C‐terminal halves of TRAF proteins means that when receptors cluster, it is presumed that RING dimers connect TRAF trimers to form a network. Here, using purified TRAF6 proteins, we provide direct evidence in support of this model, and we show that TRAF6 trimers bind Lys63‐linked ubiquitin chains to promote their processive assembly. This study provides critical evidence in support of TRAF trimers as key players in signalling.