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Publication Abstract from PubMed

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 kinase) and SPAK (serine/threonine proline-alanine-rich kinase) 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 (1)H,(15)N heteronuclear single quantum coherence spectra. Mutations to the WNK1-AI and binding peptides confirm a similar binding mode.

Solution Structure of the WNK1 Autoinhibitory Domain, a WNK-Specific PF2 Domain.,Moon TM, Correa F, Kinch LN, Piala AT, Gardner KH, Goldsmith EJ J Mol Biol. 2013 Jan 30. pii: S0022-2836(13)00047-8. doi:, 10.1016/j.jmb.2013.01.031. PMID:23376100^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.