Adam Frost from the University of Utah, School of Medicine.

Host: Chris Fromme.

Title: Structure and function of a human ESCRT-III assembly that drives cell division.

Abstract: How does the ESCRT machinery engage cellular membranes in order to draw the necks of budding viruses, vesicles, and intercellular bridges together? This is the fundamental and still outstanding question that we are studying with in vitro reconstitution, high-resolution visualization, and structure determination via electron cryo-microscopy (cryoEM). Studies from a number of laboratories have established that ESCRT-III family proteins form filaments that are intimately involved in these membrane remodeling processes. Although crystal structures are available for ESCRT-III proteins in monomeric and presumably auto-inhibited conformations, the molecular architecture of polymeric and membrane-bound ESCRT-III filaments has not yet been established. I will present a pseudo-atomic cryo-EM reconstruction of the helical filaments formed by the co-assembly of an ESCRT-III hetero-dimeric pair: IST1 and CHMP1B. The reconstruction demonstrates that IST1 and CHMP1B copolymerize as a heterodimer into a novel membrane-molding helical filament. Formation of the heterodimer and polymerization of the helix depends upon a dramatic domain swap in the CHMP1B subunit. I will also describe reconstitution experiments in which helical arrays of ESCRT-III filaments bind and tubulate model membranes with a topology that matches in vivo ESCRT-III-mediated membrane remodeling. Together, these experiments reveal how ESCRT-III subunits form filaments, assemble into helices, bind to and remodel cellular membranes.

Poster available