Crystal structure of the TAO2 kinase domain: Activation and specificity of a Ste20p MAP3K

Tianjun Zhou, Malavika Raman, Yan Gao, Svetlana Earnest, Zhu Chen, Mischa Machius, Melanie H. Cobb, Elizabeth J. Goldsmith

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Abstract

TAO2 is a mitogen-activated protein kinase kinase kinase (MAP3K) that doubly phosphorylates and activates the MAP kinase kinases (MAP2Ks) MEK3 and MEK6. The structure of the kinase domain of TAO2 (1-320) has been solved in its phosphorylated active conformation. The structure, together with structure-based mutagenic analysis, reveals that positively charged residues in the substrate binding groove mediate the first step in the dual phosphorylation of MEK6, on the threonine residue in the motif DS*VAKT*I (*denotes phosphorylation site) of MEK6. TAO2 is a Ste20p homolog, and the structure of active TAO2, in comparison with that of low-activity p21-activated protein kinase (PAK1), a Ste20p-related MAP4K, reveals how this group of kinases is activated by phosphorylation. Finally, active TAO2 displays unusual interactions with ATP, involving, in part, a subgroup-specific C-terminal extension of TAO2. The observed interactions may be useful in making specific inhibitors of TAO kinases.

Original languageEnglish (US)
Pages (from-to)1891-1900
Number of pages10
JournalStructure
Volume12
Issue number10
DOIs
StatePublished - Oct 2004

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Phosphotransferases
Phosphorylation
Troleandomycin
p21-Activated Kinases
MAP Kinase Kinase Kinases
Mitogen-Activated Protein Kinase Kinases
Threonine
Protein Kinases
Adenosine Triphosphate

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Crystal structure of the TAO2 kinase domain : Activation and specificity of a Ste20p MAP3K. / Zhou, Tianjun; Raman, Malavika; Gao, Yan; Earnest, Svetlana; Chen, Zhu; Machius, Mischa; Cobb, Melanie H.; Goldsmith, Elizabeth J.

In: Structure, Vol. 12, No. 10, 10.2004, p. 1891-1900.

Research output: Contribution to journalArticle

Zhou, Tianjun ; Raman, Malavika ; Gao, Yan ; Earnest, Svetlana ; Chen, Zhu ; Machius, Mischa ; Cobb, Melanie H. ; Goldsmith, Elizabeth J. / Crystal structure of the TAO2 kinase domain : Activation and specificity of a Ste20p MAP3K. In: Structure. 2004 ; Vol. 12, No. 10. pp. 1891-1900.
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AU - Machius, Mischa

AU - Cobb, Melanie H.

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