Crystal Structure of the Herpesvirus Nuclear Egress Complex Provides Insights into Inner Nuclear Membrane Remodeling
Tzviya Zeev-Ben-Mordehai,
Marion Weberruß,
Michael Lorenz,
Juliana Cheleski,
Teresa Hellberg,
Cathy Whittle,
Kamel El Omari,
Daven Vasishtan,
Kyle C. Dent,
Karl Harlos,
Kati Franzke,
Christoph Hagen,
Barbara G. Klupp,
Wolfram Antonin,
Thomas C. Mettenleiter,
Kay Grünewald
Affiliations
Tzviya Zeev-Ben-Mordehai
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Marion Weberruß
Friedrich Miescher Laboratory of the Max Planck Society, 72076 Tübingen, Germany
Michael Lorenz
Friedrich Miescher Laboratory of the Max Planck Society, 72076 Tübingen, Germany
Juliana Cheleski
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Teresa Hellberg
Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald – Insel Riems, Germany
Cathy Whittle
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Kamel El Omari
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Daven Vasishtan
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Kyle C. Dent
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Karl Harlos
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Kati Franzke
Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald – Insel Riems, Germany
Christoph Hagen
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
Barbara G. Klupp
Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald – Insel Riems, Germany
Wolfram Antonin
Friedrich Miescher Laboratory of the Max Planck Society, 72076 Tübingen, Germany
Thomas C. Mettenleiter
Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald – Insel Riems, Germany
Kay Grünewald
Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK
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.
