{PDOC52113}
{PS52113; FV_NP_CT}
{BEGIN}
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* Filovirus nucleoprotein C-terminal (NP-Ct) domain profile *
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Viral hemorrhagic  fevers  (VHFs)  constitute  a  group of severe illnesses in
which the  vascular  system  is  damaged  with accompanying internal bleeding,
while regulatory  functions  of  the  body  are  critically  impaired. Several
distinct families  of  viruses  cause  VHF, with varying disease severity. The
most dangerous  VHF,  associated with a mortality as high as 90%, is caused by
the filoviruses  (Filoviridae) [E1]. The Filoviridae family of negative-sense,
single-stranded RNA   (ssRNA)   viruses   is   comprised  of  two  species  of
Marburgvirus (MARV  and  RAVV)  and  five  species  of  Ebolavirus, i.e. Zaire
(EBOV), Reston  (RESTV),  Sudan  (SUDV), Tai Forest (TAFV, also known as Ivory
Coast) and Bundibugyo (BDBV). In each of these viruses the ssRNA encodes seven
distinct proteins,  most  of  which  have  multiple functions. Two of them are
associated with  the membrane: the glycoprotein (GP), which is a transmembrane
protein, and VP40, which is associated with the inner surface of the membrane.
The remaining  five  principal  proteins  [i.e.  the nucleoprotein (NP), VP35,
VP30, VP24  and  RNA  polymerase  (L)]  all  interact  with  ssRNA to form the
nucleocapsid. NP  is  the most abundant viral protein in the infected cell and
within the  viral nucleocapsid. It is tightly associated with the viral RNA in
the nucleocapsid,  and  during  the  lifecycle  of  the virus is essential for
transcription, RNA  replication,  genome  packaging  and nucleocapsid assembly
prior to  membrane  encapsulation. NP has an N-terminal region that is engaged
in packaging  the  ssRNA  and a C-terminal region that is largely unstructured
and which  is  implicated  in  several  protein-protein  interactions. This C-
terminal region  contains  a  unique  globular  domain  (NP-Ct) which shows no
homology to  any  known  proteins  and  is  purported to be a hub for protein-
protein interactions within the nucleocapsid. NP-Ct is necessary for formation
of inclusion bodies (IBs), cytoplasmic sites of nucleocapsid formation and RNA
replication, housing key steps in the virus life cycle. NP-Ct is also required
for the production of infectious virus-like particles (VLPs) [1,2,3].

The NP-Ct  domain  shows  relatively low amino-acid sequence conservation. Its
structure reveals  a  novel tertiary fold that is distantly reminiscent of the
beta-grasp architecture.  At  its  N-terminus,  NP-Ct contains an antiparallel
pair of  alpha-helices  (alphaA  and  alphaB)  followed  by  two  beta-strands
arranged in  an antiparallel hairpin (beta1 and beta2). A stretch of irregular
but structured  polypeptide chain leads to a short alpha-helix (alphaC) at the
other extremity  of  the  oblong  molecule,  followed  by another beta-hairpin
(beta3 and  beta4) and a C-terminal alpha-helix, alphaD. The latter appears to
be a  critical  element of the structure, as it runs through the center of the
molecule, providing  a  scaffold  around  which  most  of the remainder of the
molecule is folded. Residues that belong to the alphaD helix make contact with
the alphaB  helix,  with  both  beta-hairpins  and  with  the  coil  structure
connecting the two beta-hairpins (see <PDB:4QAZ>) [1,2].

The profile we developed covers the entire filovirus NP-Ct domain.

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

[ 1] Dziubanska P.J., Derewenda U., Ellena J.F., Engel D.A.,
     Derewenda Z.S.
     "The structure of the C-terminal domain of the Zaire ebolavirus
     nucleoprotein."
     Acta Crystallogr. D. Biol. Crystallogr. 70:2420-2429(2014).
     PubMed=25195755; DOI=10.1107/S1399004714014710
[ 2] Baker L.E., Ellena J.F., Handing K.B., Derewenda U., Utepbergenov D.,
     Engel D.A., Derewenda Z.S.
     "Molecular architecture of the nucleoprotein C-terminal domain from
     the Ebola and  Marburg viruses."
     Acta Crystallogr. D. Struct. Biol. 72:49-58(2016).
     PubMed=26894534; DOI=10.1107/S2059798315021439
[ 3] Miyake T., Farley C.M., Neubauer B.E., Beddow T.P., Hoenen T.,
     Engel D.A.
     "Ebola Virus Inclusion Body Formation and RNA Synthesis Are Controlled
     by a Novel  Domain of Nucleoprotein Interacting with VP35."
     J. Virol. 94:0-0(2020).
     PubMed=32493824; DOI=10.1128/JVI.02100-19
[E1] https://viralzone.expasy.org/23

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