Crystal structure of domain-swapped STE20 OSR1 kinase domain

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

OSR1 (oxidative stress-responsive-1) and SPAK (Ste20/Sps1-related proline/alanine-rich kinase) belong to the GCK-VI subfamily of Ste20 group kinases. OSR1 and SPAK are key regulators of NKCCs (Na +/K +/2Cl - cotransporters) and activated by WNK family members (with-no-lysine kinase), mutations of which are known to cause Gordon syndrome, an autosomal dominant form of inherited hypertension. The crystal structure of OSR1 kinase domain has been solved at 2.25 Å. OSR1 forms a domain-swapped dimer in an inactive conformation, in which P+1 loop and alpha;EF helix are swapped between dimer-related monomers. Structural alignment with nonswapped Ste20 TAO2 kinase indicates that the integrity of chemical interactions in the kinase domain is well preserved in the domain-swapped interfaces. The OSR1 kinase domain has now been added to a growing list of domain-swapped protein kinases recently reported, suggesting that the domain- swapping event provides an additional layer of complexity in regulating protein kinase activity. Published by Wiley-Blackwell.

Original languageEnglish (US)
Pages (from-to)304-313
Number of pages10
JournalProtein Science
Volume18
Issue number2
DOIs
StatePublished - Feb 2009

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Oxidative stress
Oxidative Stress
Phosphotransferases
Crystal structure
Protein Kinases
Proline
Alanine
Dimers
Lysine
Hypertension
Conformations
Mutation
Monomers

Keywords

  • Crystallography
  • Domain swapping
  • OSR1
  • STE20 kinase family

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Crystal structure of domain-swapped STE20 OSR1 kinase domain. / Lee, Seung Jae; Cobb, Melanie H.; Goldsmith, Elizabeth J.

In: Protein Science, Vol. 18, No. 2, 02.2009, p. 304-313.

Research output: Contribution to journalArticle

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AU - Cobb, Melanie H.

AU - Goldsmith, Elizabeth J.

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N2 - OSR1 (oxidative stress-responsive-1) and SPAK (Ste20/Sps1-related proline/alanine-rich kinase) belong to the GCK-VI subfamily of Ste20 group kinases. OSR1 and SPAK are key regulators of NKCCs (Na +/K +/2Cl - cotransporters) and activated by WNK family members (with-no-lysine kinase), mutations of which are known to cause Gordon syndrome, an autosomal dominant form of inherited hypertension. The crystal structure of OSR1 kinase domain has been solved at 2.25 Å. OSR1 forms a domain-swapped dimer in an inactive conformation, in which P+1 loop and alpha;EF helix are swapped between dimer-related monomers. Structural alignment with nonswapped Ste20 TAO2 kinase indicates that the integrity of chemical interactions in the kinase domain is well preserved in the domain-swapped interfaces. The OSR1 kinase domain has now been added to a growing list of domain-swapped protein kinases recently reported, suggesting that the domain- swapping event provides an additional layer of complexity in regulating protein kinase activity. Published by Wiley-Blackwell.

AB - OSR1 (oxidative stress-responsive-1) and SPAK (Ste20/Sps1-related proline/alanine-rich kinase) belong to the GCK-VI subfamily of Ste20 group kinases. OSR1 and SPAK are key regulators of NKCCs (Na +/K +/2Cl - cotransporters) and activated by WNK family members (with-no-lysine kinase), mutations of which are known to cause Gordon syndrome, an autosomal dominant form of inherited hypertension. The crystal structure of OSR1 kinase domain has been solved at 2.25 Å. OSR1 forms a domain-swapped dimer in an inactive conformation, in which P+1 loop and alpha;EF helix are swapped between dimer-related monomers. Structural alignment with nonswapped Ste20 TAO2 kinase indicates that the integrity of chemical interactions in the kinase domain is well preserved in the domain-swapped interfaces. The OSR1 kinase domain has now been added to a growing list of domain-swapped protein kinases recently reported, suggesting that the domain- swapping event provides an additional layer of complexity in regulating protein kinase activity. Published by Wiley-Blackwell.

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KW - STE20 kinase family

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