title: Crystal Structure of the Herpesvirus Nuclear Egress Complex Provides Insights into Inner Nuclear Membrane Remodeling.
abstract: Although nucleo-cytoplasmic transport is typically mediated through nuclear pore complexes, herpesvirus capsids exit the nucleus via a unique vesicular pathway. Together, the conserved herpesvirus proteins pUL31 and pUL34 form the heterodimeric nuclear egress complex (NEC), which, in turn, mediates the formation of tight-fitting membrane vesicles around capsids at the inner nuclear membrane. Here, we present the crystal structure of the pseudorabies virus NEC. The structure revealed that a zinc finger motif in pUL31 and an extensive interaction network between the two proteins stabilize the complex. Comprehensive mutational analyses, characterized both in situ and in vitro, indicated that the interaction network is not redundant but rather complementary. Fitting of the NEC crystal structure into the recently determined cryoEM-derived hexagonal lattice, formed in situ by pUL31 and pUL34, provided details on the molecular basis of NEC coat formation and inner nuclear membrane remodeling.
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Tzviya
authors.initials: T
authors.lastname: Zeev-Ben-Mordehai
authors.affiliation: Friedrich Miescher Laboratory of the Max Planck Society, 72076 Tübingen, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Weberruß
authors.affiliation: Friedrich Miescher Laboratory of the Max Planck Society, 72076 Tübingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lorenz
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Juliana
authors.initials: J
authors.lastname: Cheleski
authors.affiliation: Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald - Insel Riems, Germany.
authors.forename: Teresa
authors.initials: T
authors.lastname: Hellberg
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Cathy
authors.initials: C
authors.lastname: Whittle
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Kamel
authors.initials: K
authors.lastname: El Omari
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Daven
authors.initials: D
authors.lastname: Vasishtan
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Kyle C
authors.initials: KC
authors.lastname: Dent
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Karl
authors.initials: K
authors.lastname: Harlos
authors.affiliation: Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald - Insel Riems, Germany.
authors.forename: Kati
authors.initials: K
authors.lastname: Franzke
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hagen
authors.affiliation: Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald - Insel Riems, Germany.
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Klupp
authors.affiliation: Friedrich Miescher Laboratory of the Max Planck Society, 72076 Tübingen, Germany. Electronic address: wolfram.antonin@tuebingen.mpg.de.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Antonin
authors.affiliation: Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald - Insel Riems, Germany.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Mettenleiter
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK. Electronic address: kay@strubi.ox.ac.uk.
authors.forename: Kay
authors.initials: K
authors.lastname: Grünewald
mesh_terms: D021581:Active Transport, Cell Nucleus; D018360:Crystallography, X-Ray; D006564:Herpesviridae / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009685:Nuclear Envelope / Q000737:chemistry* / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D009687:Nuclear Proteins; D014764:Viral Proteins