Nuclear Egress Complexes of HCMV and Other Herpesviruses: Solving the Puzzle of Sequence Coevolution, Conserved Structures and Subfamily-Spanning Binding Properties

Marschall M, Häge S, Conrad M, Alkhashrom S, Kicuntod J, Schweininger J, Kriegel M, Loesing J, Tillmanns J, Neipel F, Eichler J, Muller Y, Sticht H (2020)

Publication Type: Journal article, Review article

Publication year: 2020

Journal

Viruses MDPI

Book Volume: 12

Journal Issue: 6

DOI: 10.3390/v12060683

Abstract

Herpesviruses uniquely express two essential nuclear egress-regulating proteins forming a heterodimeric nuclear egress complex (core NEC). These core NECs serve as hexameric lattice-structured platforms for capsid docking and recruit viral and cellular NEC-associated factors that jointly exert nuclear lamina as well as membrane-rearranging functions (multicomponent NEC). The regulation of nuclear egress has been profoundly analyzed for murine and human cytomegaloviruses (CMVs) on a mechanistic basis, followed by the description of core NEC crystal structures, first for HCMV, then HSV-1, PRV and EBV. Interestingly, the highly conserved structural domains of these proteins stand in contrast to a very limited sequence conservation of the key amino acids within core NEC-binding interfaces. Even more surprising, although a high functional consistency was found when regarding the basic role of NECs in nuclear egress, a clear specification was identified regarding the limited, subfamily-spanning binding properties of core NEC pairs and NEC multicomponent proteins. This review summarizes the evolving picture of the relationship between sequence coevolution, structural conservation and properties of NEC interaction, comparing HCMV to alpha-, beta- and gamma-herpesviruses. Since NECs represent substantially important elements of herpesviral replication that are considered as drug-accessible targets, their putative translational use for antiviral strategies is discussed.

Authors with CRIS profile

Manfred Marschall Medizinische Fakultät Sigrun Häge Institute of Clinical and Molecular Virology Marcus Conrad Professur für Bioinformatik Sewar Alkhashrom Lehrstuhl für Pharmazeutische Chemie Johannes Schweininger Lehrstuhl für Biotechnik (Proteinstruktur und -design) Mark Kriegel Lehrstuhl für Biotechnik (Proteinstruktur und -design) Frank Neipel Institute of Clinical and Molecular Virology Jutta Eichler Professur für Pharmazeutische Chemie Yves Muller Lehrstuhl für Biotechnik (Proteinstruktur und -design) Heinrich Sticht Professur für Bioinformatik

How to cite

APA:

Marschall, M., Häge, S., Conrad, M., Alkhashrom, S., Kicuntod, J., Schweininger, J.,... Sticht, H. (2020). Nuclear Egress Complexes of HCMV and Other Herpesviruses: Solving the Puzzle of Sequence Coevolution, Conserved Structures and Subfamily-Spanning Binding Properties. Viruses, 12(6). https://dx.doi.org/10.3390/v12060683

MLA:

Marschall, Manfred, et al. "Nuclear Egress Complexes of HCMV and Other Herpesviruses: Solving the Puzzle of Sequence Coevolution, Conserved Structures and Subfamily-Spanning Binding Properties." Viruses 12.6 (2020).

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