EZRIN: A KEY PROTEIN THAT CONTROLS THE STRUCTURE OF HUMAN CELL MEMBRANES
Abstract
All cells are surrounded by a plasma membrane. For healthy function, individual cells must control theshape of this protective barrier. Underlying the plasma membrane is a filamentous protein structure calledthe cortical cytoskeleton. This is a dynamic, active structure that can generate forces and change its shapevia the action of motor proteins. The cortical cytoskeleton controls the shape of the plasma membrane,facilitating the formation of membrane-bound vesicles that import cargo and the fusion of intracellularvesicles with the plasma membrane that export cargo. The coupling between the cortical cytoskeleton andthe plasma membrane is mediated by a family of proteins, the ERMs: ezrin, radixin and moesin. ERMproteins are a unique feature of all animal cells, and their structure is highly conserved. How ERMproteins couple the cytoskeleton to target membranes is currently unknown. Using cryo-electronmicroscopy, we will determine the atomic structure of the human ERM protein ezrin while bound to atarget membrane. Our preliminary data indicate that this structure will differ significantly from that offree ezrin, which we have previously determined by x-ray crystallography. By comparing the two statesof ezrin, we will understand how ezrin targets specific membranes and how it transmits forces betweenthe cortical cytoskeleton and the membrane. Our initial cryo-electron microscopy images of ezrin boundto membrane vesicles indicate that ezrin self-assembles on the membrane surface. These assemblies alterthe shape of the membrane, creating facets on the otherwise spherical vesicles. We aim to determine thestructure of these membrane-bound arrays of ezrin in order to understand their collective properties thatmodulate membrane structure. Ezrin malfunction is associated with metastasis in human cancer. Theincrease in understanding normal ezrin function that results from our atomic structures will provideinsight into pathologies associated with metastasis.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2023
- Source ID
- FA23862114101
Entities
People
- Paul Curmi
Organizations
- Air Force Office of Scientific Research
- United States Air Force
- University of New South Wales