{PDOC52110}
{PS52110; FV_VP35_CC_OD}
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* Filoviruses viral protein 35 (VP35) coiled-coil oligomerization domain (OD) profile *
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The Ebolavirus (EBOV) and Marburgvirus (MARV) belong to the Filoviridae family
[E1], a  group  of  filamentous, single-stranded, negative-sensed RNA viruses.
Upon infection,  uncontrolled  propagation  of  EBOV  and  MARV  causes severe
hemorrhagic fevers with high mortality rates. So far, six species of EBOV have
been identified, including Bundibugyo, Reston, Sudan, Tai Forest, Bombali, and
Zaire Ebolavirus, while Lake Victoria Marburgvirus is the only member in MARV.
The genomes   of  MARV  and  EBOV  encode  seven  viral  proteins  in  tandem:
nucleoprotein (N),  viral protein (VP35), VP40, glycoprotein (GP), VP30, VP24,
and large protein (L). The viral genome is encapsidated by N proteins, forming
a helical   nucleocapsid   that   serves   as  template  for  replication  and
transcription. These  processes  are  critical to the viral life cycle and are
facilitated by  the RNA-dependent RNA polymerase (RdRp) complex, consisting of
the L protein and its essential cofactor VP35. L contains all of the enzymatic
activity required  for  RNA transcription and replication. Filovirus VP35 is a
multifunctional protein,  which acts as a polymerase cofactor, a viral protein
chaperone, and an antagonist of the innate immune response. The filovirus VP35
N-terminal region contains an nucleoprotein (NP) binding peptide (NPBP), which
regulates NP oligomerization and ssRNA binding, followed by an oligomerization
domain (OD) that bridges the interaction between NP and L polymerase important
for RNA  synthesis. The C-terminal interferon (IFN) inhibitory domain (IID) is
largely responsible  for  innate  immune  antagonism  (see <PDOC51735>). Homo-
oligomerization of  VP35  through  ODs  is essential for its function in viral
replication and  transcription as well as maximizing the interferon-antagonist
activity [1,2,3,4,5].

Despite low   amino   acid   identity   between  EBOV  and  MARV  VP35,  their
oligomerization domains   both   assemble   into  coiled-coil  oligomers  (see
<PDB:5TOI>). The  oligomerization  domains  of  both  the  MARV  and EBOV VP35
proteins are composed of coiled coils flanked at both ends by proline residues
and additional   helical  secondary  structures.  These  coiled-coil  flanking
prolines are  conserved  across  MARVs  and most of the EBOVs, suggesting that
these hinge   points   may  be  functionally  important.  MARV  and  EBOV  may
oligomerize differently:  MARV as a trimer and EBOV as a tetramer. Differences
in the  oligomeric states of the MARV and EBOV VP35 proteins may contribute to
the observed  variations  in RNA binding preferences. EBOV VP35 binds RNA in a
cooperative manner, utilizing an asymmetric dimer of C-terminal domains (CTDs)
to cap  the ends of dsRNA before coating the dsRNA backbone. No such dimer has
been observed in any of the MARV VP35 structures solved to date, and MARV VP35
does not  require  capping  in  order  to  coat  dsRNA.  It is possible that a
tetrameric VP35  is  better  adapted  to  form these CTD dimers because of the
slightly increased  avidity that would be facilitated by the higher oligomeric
state of the overall protein [3,4,5].

The profile we developed covers the entire VP35 coiled-coil OD domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: June 2026 / First entry.

[ 1] Li G., Du T., Wang J., Jie K., Ren Z., Zhang X., Zhang L., Wu S.,
     Ru H.
     "Structural insights into the RNA-dependent RNA polymerase complexes
     from highly  pathogenic Marburg and Ebola viruses."
     Nat. Commun. 16:3080-3080(2025).
     PubMed=40164610; DOI=10.1038/s41467-025-58308-1
[ 2] Uwase G., Luthra P., Vogel O.A., Batra J., La Rosa B.A.,
     Sheehan K.C.F., Khatavkar O., Payton J.E., Davey R.A., Krogan N.J.,
     Basler C.F., Leung D.W., Amarasinghe G.K.
     "Ebola virus VP35 NNLNS motif modulates viral RNA synthesis and
     MIB2-mediated  signaling."
     Proc. Natl. Acad. Sci. U. S. A. 122:E2411961122-E2411961122(2025).
     PubMed=40982696; DOI=10.1073/pnas.2411961122
[ 3] Uwase G., Leung D.W., Amarasinghe G.K.
     "25 Years of Ebola Virus VP35 Research."
     J. Mol. Biol. 437:169366-169366(2025).
     PubMed=40752869; DOI=10.1016/j.jmb.2025.169366
[ 4] Reid S.P., Cardenas W.B., Basler C.F.
     "Homo-oligomerization facilitates the interferon-antagonist activity
     of the  ebolavirus VP35 protein."
     Virology 341:179-189(2005).
     PubMed=16095644; DOI=10.1016/j.virol.2005.06.044
[ 5] Bruhn J.F., Kirchdoerfer R.N., Urata S.M., Li S., Tickle I.J.,
     Bricogne G., Saphire E.O.
     "Crystal Structure of the Marburg Virus VP35 Oligomerization Domain."
     J. Virol. 91:0-0(2017).
     PubMed=27847355; DOI=10.1128/JVI.01085-16
[E1! https://viralzone.expasy.org/23

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