Solution structure of the WNK1 autoinhibitory domain, a WNK-specific PF2 domain

Thomas M. Moon, Fernando Correa, Lisa N. Kinch, Alexander T. Piala, Kevin H. Gardner, Elizabeth J. Goldsmith

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

WNK1 [with no lysine (K)-1] is a 250-kDa serine/threonine protein kinase involved in the maintenance of cellular salt levels and is directly linked to a hereditary form of hypertension. Here, we report the solution NMR structure of the autoinhibitory domain of WNK1 (WNK1-AI), a small regulatory subunit that lies immediately C-terminal of the kinase domain. We show that this domain is a homolog of the RFXV-binding PASK/FRAY homology 2 (PF2) domain found in OSR (oxidative stress responsive) and SPAK (serine/threonine proline-alanine-rich) kinases, which are substrates of WNK1. The WNK1-AI has a circularly permuted topology relative to the OSR1-PF2 domain. Nevertheless, like PF2 domains, WNK1-AI binds peptides that contain an RFXV motif with micromolar affinities as assessed by changes in 1H,15N heteronuclear single quantum coherence spectra. Mutations to the WNK1-AI and binding peptides confirm a similar binding mode.

Original languageEnglish (US)
Pages (from-to)1245-1252
Number of pages8
JournalJournal of Molecular Biology
Volume425
Issue number8
DOIs
StatePublished - Apr 26 2013

Fingerprint

Phosphotransferases
Peptides
Protein-Serine-Threonine Kinases
Threonine
Proline
Alanine
Serine
Lysine
Oxidative Stress
Salts
Maintenance
Hypertension
Mutation

Keywords

  • autoinhibitory domain
  • NMR
  • PF2
  • protein kinase
  • WNK1

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Solution structure of the WNK1 autoinhibitory domain, a WNK-specific PF2 domain. / Moon, Thomas M.; Correa, Fernando; Kinch, Lisa N.; Piala, Alexander T.; Gardner, Kevin H.; Goldsmith, Elizabeth J.

In: Journal of Molecular Biology, Vol. 425, No. 8, 26.04.2013, p. 1245-1252.

Research output: Contribution to journalArticle

Moon, Thomas M. ; Correa, Fernando ; Kinch, Lisa N. ; Piala, Alexander T. ; Gardner, Kevin H. ; Goldsmith, Elizabeth J. / Solution structure of the WNK1 autoinhibitory domain, a WNK-specific PF2 domain. In: Journal of Molecular Biology. 2013 ; Vol. 425, No. 8. pp. 1245-1252.
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AU - Goldsmith, Elizabeth J.

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