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 the shape of this protective barrier. Underlying the plasma membrane is a filamentous protein structure called the cortical cytoskeleton. This is a dynamic, active structure that can generate forces and change its shape via 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 intracellular vesicles with the plasma membrane that export cargo. The coupling between the cortical cytoskeleton and the plasma membrane is mediated by a family of proteins, the ERMs: ezrin, radixin and moesin. ERM proteins are a unique feature of all animal cells, and their structure is highly conserved. How ERM proteins couple the cytoskeleton to target membranes is currently unknown. Using cryo-electron microscopy, we will determine the atomic structure of the human ERM protein ezrin while bound to a target membrane. Our preliminary data indicate that this structure will differ significantly from that of free ezrin, which we have previously determined by x-ray crystallography. By comparing the two states of ezrin, we will understand how ezrin targets specific membranes and how it transmits forces between the cortical cytoskeleton and the membrane. Our initial cryo-electron microscopy images of ezrin bound to membrane vesicles indicate that ezrin self-assembles on the membrane surface. These assemblies alter the shape of the membrane, creating facets on the otherwise spherical vesicles. We aim to determine the structure of these membrane-bound arrays of ezrin in order to understand their collective properties that modulate membrane structure. Ezrin malfunction is associated with metastasis in human cancer. The increase in understanding normal ezrin function that results from our atomic structures will provide insight into pathologies associated with metastasis.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 10, 2022
- Source ID
- FA23862114101XX0
Entities
People
- Paul Curmi
Organizations
- Air Force Office of Scientific Research
- United States Air Force
- University of New South Wales