Structural insight into the assembly of human anti-HIV dynamin-like protein MxB/Mx2

Bo Xu, Jia Kong, Xin Wang, Wei Wei, Wei Xie, Xiao Fang Yu

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Interferon (IFN) is a key component of the innate immune response to exogenous pathogens. Interferon increases the mRNA levels of interferon-stimulated genes (ISGs) in vivo, which is thought to account for its antiviral activity. Recent studies have indicated that human myxovirus resistance protein 2 (Mx2 or MxB), one of these ISGs, contributes to the inhibition of HIV-1 replication by interferon. MxB may bind to HIV-1 relatively late in the post-entry phase, and it leads to a reduced level of integrated viral DNA, thereby restricting HIV-1 infection. The N-terminal 91-aa domain of MxB and the assembly of MxB mediated by the Stalk domain have also been shown to be indispensible for MxB's anti-viral functions, but the mechanism involved has remained elusive. Here, we report the crystal structure (2.9 Å) of the human MxB Stalk domain. MxB Stalk shows one dimer in the asymmetric unit. Each monomer contains a four-helix bundle. Interestingly, analyses of MxB dimer interfaces show that the majority of residues involved in the interface are not conserved between MxB and MxA, contributing to the building of a more stable MxB dimer. MxA and MxB Stalk domains share 46.7% sequence identity, and the structure of the MxA Stalk domain and the overall structure of MxB Stalk have a similar conformation. Our results indicate that although human Mx proteins share common structural characteristics, their dimerization strategies are unique, contributing to their unique contributions to viral restriction.

Original languageEnglish (US)
Pages (from-to)197-201
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume456
Issue number1
DOIs
StatePublished - Jan 2 2015

Keywords

  • Anti-HIV activity
  • Crystal structure
  • Dynamin-like protein
  • MxB
  • Stalk domain

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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