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

Yogesh Kulathu; Masato Akutsu; Anja Bremm; Kay Hofmann; David Komander

doi:10.1038/nsmb.1731

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

Yogesh Kulathu, Masato Akutsu, Anja Bremm, Kay Hofmann, David Komander

Research output: Contribution to journal › Article › peer-review

156 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1328-1330
Number of pages	3
Journal	Nature Structural and Molecular Biology
Volume	16
Issue number	12
DOIs	https://doi.org/10.1038/nsmb.1731
Publication status	Published - 2009 Dec
Externally published	Yes

ASJC Scopus subject areas

Structural Biology
Molecular Biology

Access to Document

10.1038/nsmb.1731

Cite this

@article{29d74edd2e6f4582ba47fe4dadf2d9e8,

title = "Two-sided ubiquitin binding explains specificity of the TAB2 NZF domain",

abstract = "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.",

author = "Yogesh Kulathu and Masato Akutsu and Anja Bremm and Kay Hofmann and David Komander",

note = "Funding Information: We would like to thank P. Cohen (Medical Research Council Protein Phosphorylation Unit), H. Scheel (Miltenyi Biotec), D.Veprintsev,A. Pobbati, R.Williams, O. Perisic, F. Gorrec,Y.Ye (Medical Research Council Laboratory of Molecular Biology) for help and reagents.Y.K., M.A. and A.B. are Medical Research Council Career Development Fellows.",

year = "2009",

month = dec,

doi = "10.1038/nsmb.1731",

language = "English",

volume = "16",

pages = "1328--1330",

journal = "Nature Structural and Molecular Biology",

issn = "1545-9993",

publisher = "Nature Publishing Group",

number = "12",

}

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

N1 - Funding Information: We would like to thank P. Cohen (Medical Research Council Protein Phosphorylation Unit), H. Scheel (Miltenyi Biotec), D.Veprintsev,A. Pobbati, R.Williams, O. Perisic, F. Gorrec,Y.Ye (Medical Research Council Laboratory of Molecular Biology) for help and reagents.Y.K., M.A. and A.B. are Medical Research Council Career Development Fellows.

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 - http://www.scopus.com/inward/record.url?scp=71449095149&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=71449095149&partnerID=8YFLogxK

U2 - 10.1038/nsmb.1731

DO - 10.1038/nsmb.1731

M3 - Article

C2 - 19935683

AN - SCOPUS:71449095149

SN - 1545-9993

VL - 16

SP - 1328

EP - 1330

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

IS - 12

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this