How a protein shapes the cell membrane
Our cells’ membranes have many functions. They not only provide mechanical protection, but also precisely control which substances enter or leave the cells. If they fail to perform these tasks, disease can result. Their structure is correspondingly complex: The outer cell membrane, for example, often features bottle-shaped invaginations called caveolae. Among others, they protect the cells of blood vessels, which are frequently exposed to strong mechanical forces. In addition, caveolae serve as signaling centers that help regulate blood pressure. Cells also absorb nutrients — especially fatty acids — via caveolae.
Researchers at the Max Delbrück Center have now discovered how caveolae — which are found in nearly all cells of our body — are stabilized to the outer cell membrane. “A chain of protein molecules wraps around the neck of these bottle-shaped structures to support them,” explains Dr. Oliver Daumke, Group Leader of the Structural Biology of Membrane-Associated Processes lab. Together with Dr. Misha Kudryashev, Group Leader of the In Situ Structural Biology lab, they have now elucidated the structure of this protein chain. Daumke had previously shown that without the protein EHD2 — of which the chain is composed — caveolae are not securely anchored in the cell membrane.
The authors hope that the new study could help, for example, to regulate fat uptake by cells and thus lead to better treatment of lipid metabolism disorders. The work is published in “Nature Communications.” Most of the experiments were conducted by first author Dr. Elena Vázquez-Sarandeses, a former doctoral student in Daumke’s lab, and Dr. Vasilii Mikirtumov, a former doctoral student in Kudryashev’s lab.
A chain with many links
Kudryashev and his team have developed new cryo-electron microscopy methods, which enabled them to resolve how two molecules of the EHD2 protein combine to form a dimer, thereby creating the individual chain links. “Certain parts of these EHD2 links then attach to one another, forming a chain,” explains Vázquez-Sarandeses. “We were able to observe how this chain wrapped itself around the tubular membrane structures we used for our experiments.”
EHD2 is a protein composed of 540 amino acids. As the researchers have now discovered, the first 19 amino acids act as a spacer. They ensure that only one chain at a time wraps around the neck of the caveolae. “Without it, multiple chains align side by side, causing the caveolae to lose their typical shape and function,” says Daumke. And without functioning EHD2 chains, the bottlenecks become increasingly thinner and longer and eventually detach from the cell membrane.
“This study was technically very challenging. But it helps us understand how proteins come together to perform a specific task within the cell — in other words, how molecular functions become cellular functions,” Daumke adds. This is a key focus of Helmholtz research.
Essential for muscles, the heart and blood vessels
Next, the scientists will try to visualize the EHD2 chains in living cells — precisely at the neck of a caveola. “If we succeed, we’ll also examine the protein chains in cells with altered caveola function. Then we might better understand the resulting diseases,” Daumke says.
In addition to lipid metabolism disorders, defective caveolae can cause diseases of the muscles, blood vessels, heart, lungs, and kidneys. “Without these invaginations, cells are less able to withstand mechanical stress. They’re also less able to regulate signaling processes,” explains Daumke. “That’s why tissues such as muscles, the heart, and blood vessels — which are constantly exposed to stress — are particularly vulnerable.”
Text: Anke Brodmerkel
Further information
Literature
Elena Vázquez-Sarandeses, Vasilii Mikirtumov, Jeffrey Noël, et al. (2026): “Structures of EHD2 filaments on curved membranes provide a model for caveolar neck stabilization.” Nature Communications, DOI: 10.1038/s41467-026 – 76288‑8
Contacts
Prof. Dr. Oliver Daumke
Group Leader
Structural Biology of Membrane-Associated Processes lab
Max Delbrück Center
oliver.daumke@mdc-berlin.de
Jana Schlütter
Deputy Head
Communications & Marketing
Max Delbrück Center
+49 30 9406 – 2118
Jana.Schluetter@mdc-berlin.de oder presse@mdc-berlin.de
- Max Delbrück Center
The Max Delbrück Center for Molecular Medicine in the Helmholtz Association lays the foundation for the medicine of tomorrow through today’s discoveries. At locations in Berlin-Buch, Berlin-Mitte, Heidelberg, and Mannheim, interdisciplinary teams investigate the complexity of disease at the systems level – from molecules and cells to organs and entire organisms. Together with academic, clinical, and industry partners, and as part of global networks, we turn biological insights into innovations for early detection, personalized therapies, and disease prevention. Founded in 1992, the Max Delbrück Center is home to a vibrant, international research community of around 1,800 people from over 70 countries. We are 90 percent funded by the German federal government and 10 percent by the state of Berlin.
