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The intracellular l...
The intracellular lipid-binding domain of human Na+/H+ exchanger 1 forms a lipid-protein co-structure essential for activity
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- Hendus-Altenburger, Ruth (författare)
- Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark; Cell Biology and Physiology, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen Ø, Denmark
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- Vogensen, Jens (författare)
- Cell Biology and Physiology, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen Ø, Denmark
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- Pedersen, Emilie Skotte (författare)
- Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark
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- Luchini, Alessandra (författare)
- Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen Ø, Denmark
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- Araya-Secchi, Raul (författare)
- Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen Ø, Denmark
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- Bendsoe, Anne H (författare)
- Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark; Cell Biology and Physiology, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen Ø, Denmark
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- Prasad, Nanditha Shyam (författare)
- Cell Biology and Physiology, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen Ø, Denmark
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- Prestel, Andreas (författare)
- Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark
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- Cardenas, Marité (författare)
- Malmö universitet,Institutionen för biomedicinsk vetenskap (BMV),Biofilms Research Center for Biointerfaces
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- Pedraz-Cuesta, Elena (författare)
- Cell Biology and Physiology, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen Ø, Denmark
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- Arleth, Lise (författare)
- Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen Ø, Denmark
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- Pedersen, Stine F (författare)
- Cell Biology and Physiology, Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen Ø, Denmark
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- Kragelund, Birthe B (författare)
- Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark
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(creator_code:org_t)
- 2020-12-03
- 2020
- Engelska.
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Ingår i: Communications Biology. - : Nature Publishing Group. - 2399-3642. ; 3:1
- Relaterad länk:
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https://doi.org/10.1...
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https://mau.diva-por... (primary) (Raw object)
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Abstract
Ämnesord
Stäng
- Dynamic interactions of proteins with lipid membranes are essential regulatory events in biology, but remain rudimentarily understood and particularly overlooked in membrane proteins. The ubiquitously expressed membrane protein Na+/H+-exchanger 1 (NHE1) regulates intracellular pH (pHi) with dysregulation linked to e.g. cancer and cardiovascular diseases. NHE1 has a long, regulatory cytosolic domain carrying a membrane-proximal region described as a lipid-interacting domain (LID), yet, the LID structure and underlying molecular mechanisms are unknown. Here we decompose these, combining structural and biophysical methods, molecular dynamics simulations, cellular biotinylation- and immunofluorescence analysis and exchanger activity assays. We find that the NHE1-LID is intrinsically disordered and, in presence of membrane mimetics, forms a helical αα-hairpin co-structure with the membrane, anchoring the regulatory domain vis-a-vis the transport domain. This co-structure is fundamental for NHE1 activity, as its disintegration reduced steady-state pHi and the rate of pHi recovery after acid loading. We propose that regulatory lipid-protein co-structures may play equally important roles in other membrane proteins.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
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Hendus-Altenburg ...
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Vogensen, Jens
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Pedersen, Emilie ...
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Luchini, Alessan ...
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Araya-Secchi, Ra ...
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Bendsoe, Anne H
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Prasad, Nanditha ...
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Prestel, Andreas
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Cardenas, Marité
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Pedraz-Cuesta, E ...
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Arleth, Lise
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Pedersen, Stine ...
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Kragelund, Birth ...
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Malmö universitet