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 journalArticlepeer-review

10 Scopus citations


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
Issue number8
StatePublished - Apr 26 2013


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

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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