Encephalomyocarditis virus Leader protein hinge domain is responsible for interactions with Ran GTPase

Journal Article · Thu Aug 15 04:00:00 EDT 2013 · Virology

DOI:https://doi.org/10.1016/J.VIROL.2013.05.002· OSTI ID:22436631

Encephalomyocarditis virus (EMCV), a Cardiovirus, initiates its polyprotein with a short 67 amino acid Leader (L) sequence. The protein acts as a unique pathogenicity factor, with anti-host activities which include the triggering of nuclear pore complex hyperphosphorylation and direct binding inhibition of the active cellular transport protein, Ran GTPase. Chemical modifications and protein mutagenesis now map the Ran binding domain to the L hinge-linker region, and in particular, to amino acids 35–40. Large deletions affecting this region were shown previously to diminish Ran binding. New point mutations, especially K35Q, D37A and W40A, preserve the intact L structure, abolish Ran binding and are deficient for nucleoporin (Nup) hyperphosphorylation. Ran itself morphs through multiple configurations, but reacts most effectively with L when in the GDP format, preferably with an empty nucleotide binding pocket. Therefore, L:Ran binding, mediated by the linker-hinge, is a required step in L-induced nuclear transport inhibition. - Highlights: • The hinge domain provides critical residues in Cardiovirus L:Ran complex formation. • Leader prefers to bind Ran in a nucleotide free, GDP-conformation. • L-induced Nup62 phosphorylation is reduced with Ran-deficient binding mutations.

• OSTI ID: 22436631
• Journal Information: Virology, Journal Name: Virology Journal Issue: 1 Vol. 443; ISSN VIRLAX; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINO ACIDS
GENE MUTATIONS
INHIBITION
MUTAGENESIS
NEM
PHOSPHATES
PHOSPHORYLATION
PROTEINS
RESIDUES
VIRUSES