Molecule of the Month: ESCRT-III

Membranes are the walls that structure our cells, forming a protective barrier around each cell and forming compartments such as the nucleus inside. However, membranes are not fixed like the walls in our houses. Cells constantly modify their membranes to respond to their minute-by-minute needs, shaping compartments correctly and controlling the traffic between different compartments. ESCRT proteins help with this process, remodeling membranes and pinching off pieces to form vesicles. This role is reflected in their name: “Endosomal Sorting Complexes Required for Transport.” ESCRT-III plays the central role, providing the force that’s necessary to remodel cell membranes.

Our cells build several different types of ESCRT-III proteins for different functions. The one shown here (PDB ID 6tz4) assembles into helices or spirals that form a collar around a tubular section of membrane. This large assembly is a combination of two proteins: CHMP1B and IST1. Together they form a narrow constriction at the center that thins the membrane and ultimately pinches it off. This process is used, for example, to bud small vesicles from a larger endosome compartment.

Amazingly, many types of ESCRT-III work in the opposite way, pulling membranes around the outside of the helix like a sleeve. In this way, they constrict membranes from the inside, as seen in the picture in the section below. This inside-out mechanism plays many essential roles in our cells. For example, when a cell divides, ESCRT-III helps narrow the final connection, allowing the two daughter cells to separate. Similarly, ESCRT-III seals up holes in membranes and helps repair subcellular wounds. It’s also important in managing cell-specific membrane shapes such as the long extensions of cilia and the branched structures of nerve cells.

HIV-1 hijacks the ESCRT system and forces it to assist with the final steps of the viral life cycle. As the virus buds from the surface of the infected cell, ESCRT-III narrows the neck connecting the virus to the cell, ultimately allowing the virus to pinch off and escape. As seen in this illustration by Janet Iwasa, ESCRT-III is thought to form a spiral that progressively constricts the membrane. To see the whole process, take a look at the full animation of the life cycle of HIV-1.

Proteins similar to our ESCRT-III are used in many types of cells to shape their membranes. The one shown here, VIPP1, helps manage the complex photosynthetic membranes in a cyanobacterium. Related proteins are thought to play the same role in green algae and plants. Two structures of the protein are shown here (PDB ID 7o3w and 7o3z) revealing how it forms helical assemblies of different diameters as it constricts around a membrane tubule.