Nuclear localization and intramolecular cleavage of N-terminally deleted NS5A protein of hepatitis C virus.

Abstract:

:The full-size NS5A (NS5A-F) of hepatitis C virus is localized in the cytoplasm despite the presence of a functional nuclear localization signal (NLS) in its C-terminal region (amino acids (aa) 354-362). In the present study, we demonstrated that a short stretch of sequence near the N-terminus of NS5A (aa 27-38) masked the functional NLS, preventing NS5A from being transported to the nucleus. This sequence, referred to as an NLS-masking sequence, was distinct from a nuclear export signal, as it did not actively target a protein to the cytoplasm. We also found that other sequences located at either an N- (aa 1-21) or a C-terminal region (aa 353-447) were responsible for targeting NS5A to the cytoplasm. Western blot analysis of the transfected cells revealed that NS5A mutants that had been N-terminally deleted by 66 aa or more were cleaved at a certain cleavage site, generating a common fragment of ca. 40 kDa. This result implies the possible presence of a cleavage site in the NS5A sequence around aa 150, which is exposed through conformational alteration upon the N-terminal deletions.

journal_name

Virus Res

journal_title

Virus research

authors

Song J,Nagano-Fujii M,Wang F,Florese R,Fujita T,Ishido S,Hotta H

doi

10.1016/s0168-1702(00)00206-9

subject

Has Abstract

pub_date

2000-09-25 00:00:00

pages

109-17

issue

2

eissn

0168-1702

issn

1872-7492

pii

S0168-1702(00)00206-9

journal_volume

69

pub_type

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