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Structure and eleva...
Structure and elevator mechanism of the mammalian sodium/proton exchanger NHE9
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- Winkelmann, Iven (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- Matsuoka, Rei (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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- Meier, Pascal F. (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Shutin, Denis (author)
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Zhang, Chenou (author)
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- Orellana, Laura (author)
- Karolinska Institutet,Stockholms universitet,Institutionen för biokemi och biofysik
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Sexton, Ricky (author)
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- Landreh, Michael (author)
- Karolinska Institutet
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Robinson, Carol W. (author)
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Beckstein, Oliver (author)
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- Drew, David (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Robinson, CV (author)
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(creator_code:org_t)
- 2020-10-29
- 2020
- English.
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In: EMBO Journal. - : EMBO. - 0261-4189 .- 1460-2075. ; 39:24
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Abstract
Subject headings
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- Na+/H+ exchangers (NHEs) are ancient membrane-bound nanoma- chines that work to regulate intracellular pH, sodium levels and cell volume. NHE activities contribute to the control of the cell cycle, cell proliferation, cell migration and vesicle trafficking. NHE dysfunction has been linked to many diseases, and they are targets of pharma- ceutical drugs. Despite their fundamental importance to cell home- ostasis and human physiology, structural information for the mammalian NHEs was lacking. Here, we report the cryogenic elec- tron microscopy structure of NHE isoform 9 (SLC9A9) from Equus caballus at 3.2 Å resolution, an endosomal isoform highly expressed in the brain and associated with autism spectrum (ASD) and atten- tion deficit hyperactivity (ADHD) disorders. Despite low sequence identity, the NHE9 architecture and ion-binding site are remarkably most similar to distantly related bacterial Na+/H+ antiporters with 13 transmembrane segments. Collectively, we reveal the conserved architecture of the NHE ion-binding site, their elevator-like structural transitions, the functional implications of autism disease mutations and the role of phosphoinositide lipids to promote homodimerization that, together, have important physiological ramifications.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- membrane protein
- SLCA9
- pH regulation
- sodium/proton exchanger
- structure
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Winkelmann, Iven
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Matsuoka, Rei
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Meier, Pascal F.
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Shutin, Denis
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Zhang, Chenou
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Orellana, Laura
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show more...
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Sexton, Ricky
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Landreh, Michael
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Robinson, Carol ...
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Beckstein, Olive ...
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Drew, David
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Robinson, CV
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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EMBO Journal
- By the university
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Stockholm University
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Karolinska Institutet