3A9J

Crystal structure of the mouse TAB2-NZF in complex with Lys63-linked di-ubiquitin

Summary for 3A9J

• Entry DOI: 10.2210/pdb3a9j/pdb
• Related: 3A9K
• Descriptor: Ubiquitin, Mitogen-activated protein kinase kinase kinase 7-interacting protein 2, ZINC ION, ... (5 entities in total)
• Functional Keywords: protein complex, cytoplasm, isopeptide bond, metal-binding, zinc, zinc-finger, signaling protein-metal binding protein complex, signaling protein/metal binding protein
• Biological source: Mus musculus (mouse); More
• Cellular location: Nucleus : Q99K90
• Total number of polymer chains: 3
• Total formula weight: 21224.64

Authors

Sato, Y.,Yoshikawa, A.,Yamashita, M.,Yamagata, A.,Fukai, S. (deposition date: 2009-10-29, release date: 2009-12-08, Last modification date: 2024-10-30)

Primary citation

Sato, Y.,Yoshikawa, A.,Yamashita, M.,Yamagata, A.,Fukai, S.
Structural basis for specific recognition of Lys 63-linked polyubiquitin chains by NZF domains of TAB2 and TAB3
Embo J., 28:3903-3909, 2009

PubMed Abstract: TAB2 and TAB3 activate the Jun N-terminal kinase and nuclear factor-kappaB 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 A 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.

PubMed: 19927120
DOI: 10.1038/emboj.2009.345

Experimental method

X-RAY DIFFRACTION (1.18 Å)