2lru

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Solution Structure of the WNK1 Autoinhibitory Domain

Structural highlights

2lru is a 1 chain structure with sequence from Rattus norvegicus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

WNK1_RAT Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D and SGK1. Controls sodium and chloride ion transport by inhibiting the activity of WNK4, by either phosphorylating the kinase or via an interaction between WNK4 and the autoinhibitory domain of WNK1. WNK4 regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation. WNK1 may also play a role in actin cytoskeletal reorganization. Phosphorylates NEDD4L.[1] [2]

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[3]

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

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Citations
3 reviews cite this structure
Physiological Processes Modulated by the Chloride-Sensitive WNK-SPAK/OSR1 Kinase Signaling Pathway and the Cation-Coupled Chloride Cotransporters.
Murillo-de-Ozores et al. (2020)
2 more
5 other articles
No citations found

See Also

References

  1. ↑ Yang CL, Zhu X, Ellison DH. The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase signaling complex. J Clin Invest. 2007 Nov;117(11):3403-11. PMID:17975670 doi:10.1172/JCI32033
  2. ↑ Heise CJ, Xu BE, Deaton SL, Cha SK, Cheng CJ, Earnest S, Sengupta S, Juang YC, Stippec S, Xu Y, Zhao Y, Huang CL, Cobb MH. Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no lysine (WNK) family members. J Biol Chem. 2010 Aug 13;285(33):25161-7. doi: 10.1074/jbc.M110.103432. Epub 2010, Jun 4. PMID:20525693 doi:10.1074/jbc.M110.103432
  3. ↑ Moon TM, Correa F, Kinch LN, Piala AT, Gardner KH, Goldsmith EJ. Solution Structure of the WNK1 Autoinhibitory Domain, a WNK-Specific PF2 Domain. J Mol Biol. 2013 Jan 30. pii: S0022-2836(13)00047-8. doi:, 10.1016/j.jmb.2013.01.031. PMID:23376100 doi:http://dx.doi.org/10.1016/j.jmb.2013.01.031

Contents


PDB ID 2lru

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