Can calmodulin bind to lipids of the cytosolic leaflet of plasma membranes?
Calmodulin (CaM) is a ubiquitous calcium-sensitive messenger in eukaryotic cells. It was previously shown that CaM possesses an affinity for diverse lipid moieties, including those found on CaM-binding proteins. These facts, together with our observation that CaM accumulates in membrane-rich protrusions of HeLa cells upon increased cytosolic calcium, motivated us to perform a systematic search for unmediated CaM interactions with model lipid membranes mimicking the cytosolic leaflet of plasma membranes. A range of experimental techniques and molecular dynamics simulations prove unambiguously that CaM interacts with lipid bilayers in the presence of calcium ions. The lipids phosphatidylserine (PS) and phosphatidylethanolamine (PE) hold the key to CaM-membrane interactions. Calcium induces an essential conformational rearrangement of CaM, but calcium binding to the headgroup of PS also neutralizes the membrane negative surface charge. More intriguingly, PE plays a dual role-it not only forms hydrogen bonds with CaM, but also destabilizes the lipid bilayer increasing the exposure of hydrophobic acyl chains to the interacting proteins. Our findings suggest that upon increased intracellular calcium concentration, CaM and the cytosolic leaflet of cellular membranes can be functionally connected.
Authors
- Martin Hof (ORCID: https://orcid.org/0000-0003-2884-3037)
- Piotr Jurkiewicz (ORCID: https://orcid.org/0000-0002-7823-8962)
- Marek Cebecauer (ORCID: https://orcid.org/0000-0002-4606-1218)
- Miguel Riopedre-Fernández (ORCID: https://orcid.org/0000-0001-5024-0713)
- Agnieszka Olżyńska (ORCID: https://orcid.org/0000-0001-6533-5280)
- Matti Javanainen (ORCID: https://orcid.org/0000-0003-4858-364X)
- Carmelo Tempra (ORCID: https://orcid.org/0000-0002-2890-6993)
- Pavel Jungwirth (ORCID: https://orcid.org/0000-0002-6892-3288)
- Hüseyin Evci (ORCID: https://orcid.org/0000-0001-9664-0990)
- Hector Martinez‐Seara (ORCID: https://orcid.org/0000-0001-9716-1713)
- Federica Scollo (ORCID: https://orcid.org/0000-0003-2238-006X)
- Lukasz Cwiklik (ORCID: https://orcid.org/0000-0002-2083-8738)
- Arunima Uday (ORCID: https://orcid.org/0009-0002-9787-4187)
Institutions
- University of Helsinki (FI)
- Helsinki Institute of Physics (FI)
- University of South Bohemia in České Budějovice (CZ)
- Czech Academy of Sciences, J. Heyrovský Institute of Physical Chemistry (CZ)
- Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry (CZ)
Publication Details
- Journal
- Open Biology
- Published
- 2024-09-01
- DOI
- https://doi.org/10.1098/rsob.240067
- Citations
- 2
- Primary Topic
- Lipid Membrane Structure and Behavior
- Type
- article
- Field-Weighted Citation Impact
- 0.47
Funders
- Ministerstvo Školství, Mládeže a Tělovýchovy
- Grantová Agentura České Republiky
- China Scholarship Council
- Central European Institute of Technology
- Masarykova Univerzita