10.1021/acs.biochem.8b01154.s001
Chamnongsak
Ken Chanthamontri
Chamnongsak
Ken
Chanthamontri
David S. Jordan
David S.
Jordan
Wenjie Wang
Wenjie
Wang
Chao Wu
Chao
Wu
Yanchun Lin
Yanchun
Lin
Tom J. Brett
Tom J.
Brett
Michael L. Gross
Michael L.
Gross
Daisy W. Leung
Daisy W.
Leung
The Ebola Viral Protein 35 N‑Terminus Is a
Parallel Tetramer
American Chemical Society
2018
sense RNA viruses
RNA synthesis
NNSV
virus protein 35
VP 35 functions
Ebola
eVP 35 oligomer
tetramer
Parallel Tetramer Members
evasion
role
2018-12-28 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/The_Ebola_Viral_Protein_35_N_Terminus_Is_a_Parallel_Tetramer/7575434
Members
of Mononegavirales, the order that includes nonsegmented
negative sense RNA viruses (NNSVs), encode a small number of multifunctional
proteins. In members of the Filoviridae family, virus protein 35 (VP35)
facilitates immune evasion and functions as an obligatory cofactor
for viral RNA synthesis. VP35 functions in a manner orthologous to
that of phosphoproteins from other NNSVs. Although the critical roles
of Ebola viral VP35 (eVP35) in immune evasion and RNA synthesis are
well-appreciated, a complete understanding of its organization and
its role in carrying out its many functions has yet to be fully realized.
In particular, we currently lack information about the role of the
oligomerization domain within eVP35. To address this limitation, we
report here an investigation of the oligomer structure of eVP35 using
hybrid methods that include multiangle light scattering, small-angle
X-ray scattering, and cross-linking coupled with mass spectrometry
to determine the shape and orientation of the eVP35 oligomer. Our
integrative results are consistent with a parallel tetramer in which
the N-terminal regions that are required for RNA synthesis are all
oriented in the same direction. Furthermore, these results define
a framework for targeting the symmetric tetramer for structure-based
antiviral discovery.