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  A Phosphorylated Intermediate in the Activation of WNK Kinases

Akella, R., Drozdz, M. A., Humphreys, J. M., Jiou, J., Durbacz, M. Z., Mohammed, Z. J., et al. (2020). A Phosphorylated Intermediate in the Activation of WNK Kinases. BIOCHEMISTRY, 59(18), 1747-1755. doi:10.1021/acs.biochem.0c00146.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0006-929B-6 Version Permalink: http://hdl.handle.net/21.11116/0000-0006-929C-5
Genre: Journal Article

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 Creators:
Akella, Radha1, Author
Drozdz, Mateusz A.1, Author
Humphreys, John M.1, Author
Jiou, Jenny1, Author
Durbacz, Mateusz Z.1, Author
Mohammed, Zuhair J.1, Author
He, Haixia1, Author
Liwocha, Joanna2, Author              
Sekulski, Kamil1, Author
Goldsmith, Elizabeth J.1, Author
Affiliations:
1external, ou_persistent22              
2Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society, ou_2466699              

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Free keywords: CRYSTAL-STRUCTURE; PROTEIN-KINASE; INHIBITION; MODULATION; FAMILY; DOMAIN; MODEL; LOOP
 Abstract: WNK kinases autoactivate by autophosphorylation. Crystallography of the kinase domain of WNK1 phosphorylated on the primary activating site (pWNK1) in the presence of AMP-PNP reveals a well-ordered but inactive configuration. This new pWNK1 structure features specific and unique interactions of the phosphoserine, less hydration, and smaller cavities compared with those of unphosphorylated WNK1 (uWNK1). Because WNKs are activated by osmotic stress in cells, we addressed whether the structure was influenced directly by osmotic pressure. pWNK1 crystals formed in PEG3350 were soaked in the osmolyte sucrose. Suc-WNK1 crystals maintained X-ray diffraction, but the lattice constants and pWNK1 structure changed. Differences were found in the activation loop and helix C, common switch loci in kinase activation. On the basis of these structural changes, we tested for effects on in vitro activity of two WNKs, pWNK1 and pWNK3. The osmolyte PEG400 enhanced ATPase activity. Our data suggest multistage activation of WNKs.

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Language(s): eng - English
 Dates: 2020
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: BIOCHEMISTRY
Source Genre: Journal
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Publ. Info: 1155 16TH ST, NW, WASHINGTON, DC 20036 USA : AMER CHEMICAL SOC
Pages: - Volume / Issue: 59 (18) Sequence Number: - Start / End Page: 1747 - 1755 Identifier: ISSN: 0006-2960