ArticleCrystal structure of domain-swapped STE20 OSR1 kinase domain |
| Seung-Jae Lee 1, Melanie H. Cobb 2, Elizabeth J. Goldsmith 1 * |
1Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9041
2Department of Pharmacology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9041
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| email: Elizabeth J. Goldsmith (elizabeth.goldsmith@utsouthwestern.edu) |
*Correspondence to Elizabeth J. Goldsmith, Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9041
Funded by:
U. S. Department of Energy, Office of Biological and Environmental Research; Grant Number: W-31-109-ENG-38
NIH; Grant Number: DK46993
Welch Foundation; Grant Number: I1128, I1243
| OSR1 STE20 kinase family domain swapping crystallography |
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  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. |
Received: 8 September 2008; Revised: 28 October 2008; Accepted: 30 October 2008
10.1002/pro.27
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