Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain

TY - JOUR

T1 - Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain

AU - Kulathu, Yogesh

AU - Akutsu, Masato

AU - Bremm, Anja

AU - Hofmann, Kay

AU - Komander, David

PY - 2009/12

Y1 - 2009/12

N2 - The protein kinase TAK1 is activated by binding to Lys63 (K63)-linked ubiquitin chains through its subunit TAB2. Here we analyze crystal structures of the TAB2 NZF domain bound to Lys63-linked di- and triubiquitin, revealing that TAB2 binds adjacent ubiquitin moieties via two distinct binding sites. The conformational constraints imposed by TAB2 on a Lys63 dimer cannot be adopted by linear chains, explaining why TAK1 cannot be activated by linear ubiquitination events.

AB - The protein kinase TAK1 is activated by binding to Lys63 (K63)-linked ubiquitin chains through its subunit TAB2. Here we analyze crystal structures of the TAB2 NZF domain bound to Lys63-linked di- and triubiquitin, revealing that TAB2 binds adjacent ubiquitin moieties via two distinct binding sites. The conformational constraints imposed by TAB2 on a Lys63 dimer cannot be adopted by linear chains, explaining why TAK1 cannot be activated by linear ubiquitination events.

UR - https://www.scopus.com/pages/publications/71449095149

U2 - 10.1038/nsmb.1731

DO - 10.1038/nsmb.1731

M3 - Article

C2 - 19935683

SN - 1545-9993

VL - 16

SP - 1328

EP - 1330

JO - Nature Structural & Molecular Biology

JF - Nature Structural & Molecular Biology

IS - 12

ER -