2021: Bacterial Vipp1 and PspA are members of the ancient ESCRT-III membrane-remodelling superfamily
Tree of the PspA/ESCRT-III superfamily colored according to phylogenetic groups. A long branch separates the PspA/Vipp1 (left) and ESCRT-III (right) subfamilies. Scale bar represents expected substitutions per site. Study undertaken by Diorge Souza, Tom Williams and Buzz Baum.
In all living systems, membranes are used to separate the inside of the cell from the outside environment. Membranes are also used to shape cells internally so that different areas can form specialist compartments with distinct roles. In cells, membranes are dynamic requiring continual remodelling for many processes including cell division for growth or membrane trafficking for the movement of cargo. In order to remodel the membrane, cells have evolved specialist protein families to undertake this physical work. Proteins that perform membrane remodelling and repair functions include Vipp1/IM30 in photosynthetic plastids, PspA in bacteria, and ESCRT-III in eukaryotes. ESCRT-III proteins are so ancient that they have ancestors in some archaea from which eukaryotes later evolved.
C14 symmetry Vipp1 ring showing dome-shaped curvature. The membrane binding Helix 0 can be seen lining the inner lumen.
In this project, evolutionary studies (above) showed that these protein families are homologous and share a common evolutionary origin that likely predates the last universal common ancestor (LUCA). In vitro, Vipp1 self-assembles and builds multiple polymeric forms including rings and helical tubes. In order to probe Vipp1 membrane remodelling mechanism, we recently determined the cryo-electron microscopy (cryo-EM) structure of the Vipp1 rings from the cyanobacteria Nostoc punctiforme (top of page and left movie) . The C11-C17 symmetry rings exhibited a unique asymmetric dome-shaped curvature with constricted open ends and a membrane-binding inner lumen. Each ring was built from a stack of self-organising discrete rungs where each rung constituted a Vipp1 filament in a distinct conformation. Remarkably, our evolutionary and structural data showed that both the Vipp1 subunit and the mode of filament self-assembly was conserved with ESCRT-III proteins (below). Collectively, our data suggested conserved mechanistic principles that underlie Vipp1, PspA and ESCRT-III-dependent membrane remodelling across all domains of life. Understanding how these proteins work has broad implication for cyanobacteria/plant biology and biotechnology, and human pathologies such as viral infection, antimicrobial resistance (AMR), and neurodegeneration.
Vipp1 has the same helical domain organization as ESCRT-III proteins, such as human CHMP1B shown here. In addition, Vipp1 and CHMP1B form similar polymers based on hairpin packing (blue and purple helices) and helix α5 (orange) domain swap.