Electron microscopy images of three-dimensional spirals of ESCRT-III proteins that are important for membrane remodelling reactions. Image credit: Sudeep Banjade (CC BY 4.0)
Cells are separated from the outside environment by a fatty layer called the plasma membrane. This layer not only isolates the inside of the cell from the outside, it is also essential for the cell to sense and respond to cues around it. For example, the plasma membrane contains different types of proteins that can act as receptors for signals from outside the cell or as channels to take in essential nutrients. One of the ways that the cell can respond to its environment is by recycling the proteins at the plasma membrane.
During a cell’s life, proteins from its membrane are recycled by being pulled into lysosomes, which are sacs or vesicles full of enzymes that digest these molecules. However, before reaching the lysosomes, the molecules pass through another set of vesicles called endosomes. There, ESCRT-III, a flexible scaffold made out of the proteins Snf7, Vps24 and Vps2, forms a spiral like-structure that collects the proteins and fats from the membrane. This corkscrew-like shape allows the ESCRT-III scaffold to work, but it is unclear how it is formed.
Snf7 is a protein that forms long bending chains, or “polymers”, by linking to itself. Banjade et al. found that Snf7 uses its negatively charged surface to interact with the parallel chain that Vps24 and Vps2 form at its side. However, Vps24 and Vps2 do not fit rigidly into Snf7 like a key fits in a lock. Rather, their interaction is flexible, based on charge. This flexibility may allow Vps24 and Vps2 to slide along the side of the Snf7 chain, helping to create a spiral. Banjade et al. used budding yeast as a model organism and also imaged purified proteins with electron microscopy to come upon these findings.
Understanding how ESCRT proteins interact to form complex structures may lead to a better understanding of how other membrane-bound polymers form elsewhere in the cell. ESCRT proteins are also involved in degenerative diseases, such as Alzheimer’s, where proteins that need to be recycled cannot be properly processed, and they are important for viruses such as HIV to spread between cells. Understanding how these proteins interact to form their characteristic spiral structure could potentially lead to the development of new therapies.
