Structural basis for specific recognition of Lys 63‐linked polyubiquitin chains by NZF domains of TAB2 and TAB3 |
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| Authors: | Yusuke Sato Azusa Yoshikawa Masami Yamashita Atsushi Yamagata Shuya Fukai |
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| Affiliation: | 1. Structural Biology Laboratory, Life Science Division, Synchrotron Radiation Research Organization, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan;2. Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan;3. Department of Biological Information, Tokyo Institute of Technology, Yokohama, Japan |
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| Abstract: | TAB2 and TAB3 activate the Jun N‐terminal kinase and nuclear factor‐κB pathways through the specific recognition of Lys 63‐linked polyubiquitin chains by its Npl4 zinc‐finger (NZF) domain. Here we report crystal structures of the TAB2 and TAB3 NZF domains in complex with Lys 63‐linked diubiquitin at 1.18 and 1.40 Å resolutions, respectively. Both NZF domains bind to the distal ubiquitin through a conserved Thr‐Phe dipeptide that has been shown to be important for the interaction of the NZF domain of Npl4 with monoubiquitin. In contrast, a surface specific to TAB2 and TAB3 binds the proximal ubiquitin. Both the distal and proximal binding sites of the TAB2 and TAB3 NZF domains recognize the Ile 44‐centred hydrophobic patch on ubiquitin but do not interact with the Lys 63‐linked isopeptide bond. Mutagenesis experiments show that both binding sites are required to enable binding of Lys 63‐linked diubiquitin. We therefore propose a mechanism for the recognition of Lys 63‐linked polyubiquitin chains by TAB2 and TAB3 NZF domains in which diubiquitin units are specifically recognized by a single NZF domain. |
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| Keywords: | crystallography NF‐κ B ubiquitin zinc finger |
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