Structural basis of membrane budding by the nuclear egress complex of herpesviruses.
During nuclear egress, herpesvirus capsids bud at the inner nuclear membrane forming perinuclear viral particles that subsequently fuse with the outer nuclear membrane, releasing capsids into the cytoplasm. This unusual budding process is mediated by the nuclear egress complex (NEC) composed of two conserved viral proteins, UL31 and UL34. Earlier, we discovered that the herpesvirus nuclear egress complex (NEC) could bud synthetic membranes in vitro without the help of other proteins by forming a coat-like hexagonal scaffold inside the budding membrane. To understand the structural basis of NEC-mediated membrane budding, we determined the crystal structures of the NEC from two herpesviruses. The hexagonal lattice observed in the NEC crystals recapitulates the honeycomb coats within the budded vesicles. Perturbation of the oligomeric interfaces through mutagenesis blocks budding in vitro confirming that NEC oligomerization into a honeycomb lattice drives budding. The structure represents the first atomic-level view of an oligomeric array formed by a membrane-deforming protein, making possible the dissection of its unique budding mechanism and the design of inhibitors to block it.
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA.
Janna M
JM
Bigalke
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA katya.heldwein@tufts.edu.
Ekaterina E
EE
Heldwein
D002213:Capsid / Q000378:metabolism*; D006564:Herpesviridae / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000378:metabolism; D011558:Herpesvirus 1, Suid / Q000378:metabolism; D006801:Humans; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism*; D019065:Virus Assembly / Q000502:physiology
D009687:Nuclear Proteins; C108721:UL31 protein, Human herpesvirus 1; C403420:UL34 protein, Human herpesvirus 1; D014764:Viral Proteins
UL31; UL34; herpesvirus; membrane budding; nuclear egress