کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2184474 | 1095857 | 2013 | 8 صفحه PDF | دانلود رایگان |

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.
Graphical AbstractFigure optionsDownload high-quality image (244 K)Download as PowerPoint slideHighlights
► The structure of the WNK1 autoinhibitory domain was solved by high-resolution solution NMR methods.
► The structure is similar to that of the PF2 domain of OSR, a WNK1 substrate.
► The autoinhibitory domain binds an RFXV peptide derived from the WNK1 kinase domain.
Journal: Journal of Molecular Biology - Volume 425, Issue 8, 26 April 2013, Pages 1245–1252