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J Biol Chem. 2016 May 20;291(21):11420-33. doi: 10.1074/jbc.M116.724393. Epub 2016 Mar 31.

Divergent Evolution of Nuclear Localization Signal Sequences in Herpesvirus Terminase Subunits.

Author information

1
From the Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 and.
2
From the Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107 and Institute of Biomembranes and Bioenergetics, National Research Council, Via Amendola 165/A, 70126 Bari, Italy gino.cingolani@jefferson.edu.

Abstract

The tripartite terminase complex of herpesviruses assembles in the cytoplasm of infected cells and exploits the host nuclear import machinery to gain access to the nucleus, where capsid assembly and genome-packaging occur. Here we analyzed the structure and conservation of nuclear localization signal (NLS) sequences previously identified in herpes simplex virus 1 (HSV-1) large terminase and human cytomegalovirus (HCMV) small terminase. We found a monopartite NLS at the N terminus of large terminase, flanking the ATPase domain, that is conserved only in α-herpesviruses. In contrast, small terminase exposes a classical NLS at the far C terminus of its helical structure that is conserved only in two genera of the β-subfamily and absent in α- and γ-herpesviruses. In addition, we predicted a classical NLS in the third terminase subunit that is partially conserved among herpesviruses. Bioinformatic analysis revealed that both location and potency of NLSs in terminase subunits evolved more rapidly than the rest of the amino acid sequence despite the selective pressure to keep terminase gene products active and localized in the nucleus. We propose that swapping NLSs among terminase subunits is a regulatory mechanism that allows different herpesviruses to regulate the kinetics of terminase nuclear import, reflecting a mechanism of virus:host adaptation.

KEYWORDS:

genome packaging motor; herpesvirus; importin α; nuclear translocation; nuclear transport; terminase; virus assembly; virus entry

PMID:
27033706
PMCID:
PMC4900285
DOI:
10.1074/jbc.M116.724393
[Indexed for MEDLINE]
Free PMC Article

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