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Title: Structural basis for the regulation of nuclear import of Epstein-Barr virus nuclear antigen 1 (EBNA1) by phosphorylation of the nuclear localization signal

Abstract

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is expressed in every EBV-positive tumor and is essential for the maintenance, replication, and transcription of the EBV genome in the nucleus of host cells. EBNA1 is a serine phosphoprotein, and it has been shown that phosphorylation of S385 in the nuclear localization signal (NLS) of EBNA1 increases the binding affinity to the nuclear import adaptor importin-α1 as well as importin-α5, and stimulates nuclear import of EBNA1. To gain insights into how phosphorylation of the EBNA1 NLS regulates nuclear import, we have determined the crystal structures of two peptide complexes of importin-α1: one with S385-phosphorylated EBNA1 NLS peptide, determined at 2.0 Å resolution, and one with non-phosphorylated EBNA1 NLS peptide, determined at 2.2 Å resolution. The structures show that EBNA1 NLS binds to the major and minor NLS-binding sites of importin-α1, and indicate that the binding affinity of the EBNA1 NLS to the minor NLS-binding site could be enhanced by phosphorylation of S385 through electrostatic interaction between the phosphate group of phospho-S385 and K392 of importin-α1 (corresponding to R395 of importin-α5) on armadillo repeat 8. - Highlights: • Nuclear import of EBNA1 can be regulated by phosphorylation of NLS. • Crystal structures of importin-α1 boundmore » to the NLS peptides of EBNA1 are solved. • Structures provide insights into how phosphorylation can regulate nuclear import.« less

Authors:
 [1];  [1];  [2];  [1];  [2]
  1. Division of Biological Science, Graduate School of Science, Nagoya University (Japan)
  2. (Japan)
Publication Date:
OSTI Identifier:
22696873
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 484; Journal Issue: 1; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIGENS; CRYSTAL STRUCTURE; IMPORTS; ONCOGENIC VIRUSES; PEPTIDES; PHOSPHORYLATION; REGULATIONS; SIGNALS

Citation Formats

Nakada, Ryohei, Hirano, Hidemi, Structural Biology Research Center, Graduate School of Science, Nagoya University, Matsuura, Yoshiyuki, and Structural Biology Research Center, Graduate School of Science, Nagoya University. Structural basis for the regulation of nuclear import of Epstein-Barr virus nuclear antigen 1 (EBNA1) by phosphorylation of the nuclear localization signal. United States: N. p., 2017. Web. doi:10.1016/J.BBRC.2017.01.063.
Nakada, Ryohei, Hirano, Hidemi, Structural Biology Research Center, Graduate School of Science, Nagoya University, Matsuura, Yoshiyuki, & Structural Biology Research Center, Graduate School of Science, Nagoya University. Structural basis for the regulation of nuclear import of Epstein-Barr virus nuclear antigen 1 (EBNA1) by phosphorylation of the nuclear localization signal. United States. doi:10.1016/J.BBRC.2017.01.063.
Nakada, Ryohei, Hirano, Hidemi, Structural Biology Research Center, Graduate School of Science, Nagoya University, Matsuura, Yoshiyuki, and Structural Biology Research Center, Graduate School of Science, Nagoya University. Sun . "Structural basis for the regulation of nuclear import of Epstein-Barr virus nuclear antigen 1 (EBNA1) by phosphorylation of the nuclear localization signal". United States. doi:10.1016/J.BBRC.2017.01.063.
@article{osti_22696873,
title = {Structural basis for the regulation of nuclear import of Epstein-Barr virus nuclear antigen 1 (EBNA1) by phosphorylation of the nuclear localization signal},
author = {Nakada, Ryohei and Hirano, Hidemi and Structural Biology Research Center, Graduate School of Science, Nagoya University and Matsuura, Yoshiyuki and Structural Biology Research Center, Graduate School of Science, Nagoya University},
abstractNote = {Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is expressed in every EBV-positive tumor and is essential for the maintenance, replication, and transcription of the EBV genome in the nucleus of host cells. EBNA1 is a serine phosphoprotein, and it has been shown that phosphorylation of S385 in the nuclear localization signal (NLS) of EBNA1 increases the binding affinity to the nuclear import adaptor importin-α1 as well as importin-α5, and stimulates nuclear import of EBNA1. To gain insights into how phosphorylation of the EBNA1 NLS regulates nuclear import, we have determined the crystal structures of two peptide complexes of importin-α1: one with S385-phosphorylated EBNA1 NLS peptide, determined at 2.0 Å resolution, and one with non-phosphorylated EBNA1 NLS peptide, determined at 2.2 Å resolution. The structures show that EBNA1 NLS binds to the major and minor NLS-binding sites of importin-α1, and indicate that the binding affinity of the EBNA1 NLS to the minor NLS-binding site could be enhanced by phosphorylation of S385 through electrostatic interaction between the phosphate group of phospho-S385 and K392 of importin-α1 (corresponding to R395 of importin-α5) on armadillo repeat 8. - Highlights: • Nuclear import of EBNA1 can be regulated by phosphorylation of NLS. • Crystal structures of importin-α1 bound to the NLS peptides of EBNA1 are solved. • Structures provide insights into how phosphorylation can regulate nuclear import.},
doi = {10.1016/J.BBRC.2017.01.063},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 484,
place = {United States},
year = {2017},
month = {2}
}