title: Complex formation by glycoproteins M and N of human cytomegalovirus: structural and functional aspects.
abstract: The genomes of herpesviruses contain a number of genes which are conserved throughout the family of Herpesviridae, indicating that the proteins may serve important functions in the replication of these viruses. Among these are several envelope glycoproteins, including glycoprotein M (gM) and gN, which form a complex that is covalently linked via disulfide bonds in some herpesviruses. However, deletion of gM and/or gN from most alphaherpesviruses has limited effects on replication of the respective viruses in vitro. In contrast, insertional inactivation of the gM gene of the betaherpesvirus human cytomegalovirus (HCMV) results in a replication-incompetent virus. We have started to analyze the structural and functional aspects of the interaction between gM and gN of HCMV. We show that large parts of gM are dispensable for the formation of a gM/gN complex that is transported to distal parts of the cellular secretory pathway. In addition, we demonstrate that the disulfide bond is between the cysteine at position 44 in gM and cysteine 90 in gN. However, disulfide linkage is not a prerequisite for modification and transport of the gM/gN complex. Moreover, mutant viruses that lack a disulfide bridge between gM and gN replicate with efficiencies similar to that of wild-type viruses.
authors.affiliation: Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany. mlmach@viro.med.uni-erlangen.de
authors.forename: Michael
authors.initials: M
authors.lastname: Mach
authors.forename: Barbara
authors.initials: B
authors.lastname: Kropff
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kryzaniak
authors.forename: William
authors.initials: W
authors.lastname: Britt
mesh_terms: D002460:Cell Line; D003587:Cytomegalovirus / Q000276:immunology / Q000502:physiology*; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D004220:Disulfides; C095281:UL100 protein, Cytomegalovirus; D014759:Viral Envelope Proteins; C417883:glycoprotein N, Human cytomegalovirus