Nuclear import of isoforms of the cytomegalovirus kinase pUL97 is mediated by differential activity of NLS1 and NLS2 both acting through classical importin-α binding

The Journal of General Virology
Rike WebelManfred Marschall

Abstract

The multifunctional protein kinase pUL97 of human cytomegalovirus (HCMV) strongly determines the efficiency of virus replication. Previously, the existence of two pUL97 isoforms that arise from alternative translational initiation and show a predominant nuclear localization was described. Two bipartite nuclear localization sequences, NLS1 and NLS2, were identified in the N terminus of the large isoform, whilst the small isoform exclusively contained NLS2. The current study found the following: (i) pUL97 nuclear localization in HCMV-infected primary fibroblasts showed accumulations in virus replication centres and other nuclear sections; (ii) in a quantitative evaluation system for NLS activity, the large isoform showed higher efficiency of nuclear translocation than the small isoform; (iii) NLS1 was mapped to aa 6-35 and NLS2 to aa 190-213; (iv) using surface plasmon resonance spectroscopy, the binding of both NLS1 and NLS2 to human importin-α was demonstrated, stressing the importance of individual arginine residues in the bipartite consensus motifs; (v) nuclear magnetic resonance spectroscopy of pUL97 peptides confirmed an earlier statement about the functional requirement of NLS1 embedding into an intact α-helical structure;...Continue Reading

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Citations

Jan 22, 2014·Journal of Virological Methods·Christian HeldThomas Wittenberg
Jun 28, 2014·Molecular & Cellular Proteomics : MCP·Jens MilbradtManfred Marschall
Feb 21, 2019·The Journal of Biological Chemistry·Mirjam SteingruberManfred Marschall
Sep 26, 2020·Nature Communications·Boris BogdanowLüder Wiebusch

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