Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by NZF domains of TAB2 and TAB3.

Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains.

At least eight types of ubiquitin chain exist, and individual linkages affect distinct cellular processes. The only distinguishing feature of differently linked ubiquitin chains is their structure, as polymers of the same unit are chemically identical. Here, we have crystallized Lys 63-linked and linear ubiquitin dimers, revealing that both adopt equivalent open conformations, forming no contac...

Essential roles of K63-linked polyubiquitin-binding proteins TAB2 and TAB3 in B cell activation via MAPKs.

Polyubiquitination of proteins plays a critical role in the activation of immune cells. K63-linked polyubiquitin-binding proteins TGF-β-activated kinase 1 (TAK1)-binding protein (TAB)2 and TAB3 are implicated in NF-κB signaling via TAK1 activation. However, TAB2 alone is dispensable for NF-κB activation in embryonic fibroblasts, and the functional roles of TAB2 and TAB3 in immune cells has yet ...

Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by tandem UIMs of RAP80.

RAP80 has a key role in the recruitment of the Abraxas-BRCC36-BRCA1-BARD1 complex to DNA-damage foci for DNA repair through specific recognition of Lys 63-linked polyubiquitinated proteins by its tandem ubiquitin-interacting motifs (UIMs). Here, we report the crystal structure of the RAP80 tandem UIMs (RAP80-UIM1-UIM2) in complex with Lys 63-linked di-ubiquitin at 2.2 A resolution. The two UIMs...

Specific recognition of linear ubiquitin chains by the Npl4 zinc finger (NZF) domain of the HOIL-1L subunit of the linear ubiquitin chain assembly complex.

The linear ubiquitin chain assembly complex (LUBAC) is a key nuclear factor-κB (NF-κB) pathway component that produces linear polyubiquitin chains. The HOIL-1L subunit of LUBAC has been shown to bind linear chains; however, detailed structural and functional analyses on the binding between LUBAC and linear chains have not been performed. In this study, we found that the Npl4 zinc finger (NZF) d...

TAB3 in B Cell Activation via MAPKs Polyubiquitin-Binding Proteins TAB2 and Essential Roles of K63-Linked