Biophysical Society Conference | Estes Park 2023

Membrane Budding and Fusion

Poster Abstracts

29-POS Board 10 THE UNIVERSAL SUPPRESSOR MUTATION IN THE HSV-1 NUCLEAR EGRESS COMPLEX RESTORES MEMBRANE BUDDING DEFECTS BY STABILIZING THE OLIGOMERIC LATTICE. Elizabeth B Draganova 1 ; Hui Wang 2 ; Melanie Wu 3 ; Shiqing Liao 2 ; Amber Vu 4 ; Gonzalo Gonzalez-Del Pino 1 ; Hong Zhou 2 ; Richard Roller 4 ; Ekaterina Heldwein 1 ; 1 Tufts University School of Medicine, Department of Molecular Biology and Microbiology, Boston, MA, USA 2 University of California, Los Angeles (UCLA), Department of Microbiology, Immunology & Molecular Genetics, Los Angeles , CA, USA 3 The University of Queensland, School of Chemistry and Molecular Biosciences, Brisbane, Australia 4 University of Iowa, Department of Microbiology and Immunology, Iowa City, IA, USA Nuclear egress is an essential process in herpesviral replication whereby nascent capsids translocate from the nucleus to the cytoplasm. This initial step of nuclear egress – budding at the inner nuclear membrane – is coordinated by the nuclear egress complex (NEC). Composed of the viral proteins UL31 and UL34, NEC deforms the membrane around the capsid as the latter buds into the perinuclear space. NEC oligomerization into a hexagonal membrane-bound lattice is essential for budding because mutations designed to perturb lattice interfaces reduce its budding ability. Previously, we identified an NEC suppressor mutation capable of restoring budding to a mutant with a weakened hexagonal lattice. Here, we show that the suppressor mutation can restore budding to a broad range of budding-deficient NEC mutants thereby acting as a universal suppressor. We demonstrate that the suppressor mutation indirectly promotes the formation of new contacts between the NEC hexamers that stabilize the hexagonal lattice. This stabilization strategy is powerful enough to override the otherwise deleterious effects of mutations that destabilize the NEC lattice by different mechanisms, resulting in a functional NEC hexagonal lattice and restoration of membrane budding.

82