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PDBsum entry 3vcb
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Viral protein
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PDB id
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3vcb
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References listed in PDB file
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Key reference
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Title
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Crystal structure of the c-Terminal cytoplasmic domain of non-Structural protein 4 from mouse hepatitis virus a59.
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Authors
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X.Xu,
Z.Lou,
Y.Ma,
X.Chen,
Z.Yang,
X.Tong,
Q.Zhao,
Y.Xu,
H.Deng,
M.Bartlam,
Z.Rao.
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Ref.
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Plos One, 2009,
4,
e6217.
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PubMed id
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Abstract
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BACKGROUND: The replication of coronaviruses takes place on cytoplasmic double
membrane vesicles (DMVs) originating in the endoplasmic reticulum (ER). Three
trans-membrane non-structural proteins, nsp3, nsp4 and nsp6, are understood to
be membrane anchors of the coronavirus replication complex. Nsp4 is localized to
the ER membrane when expressed alone but is recruited into the replication
complex in infected cells. It is revealed to contain four trans-membrane regions
and its N- and C-termini are exposed to the cytosol. METHODOLOGY/PRINCIPAL
FINDINGS: We have determined the crystal structures of the C-terminal
hydrophilic domain of nsp4 (nsp4C) from MHV strain A59 and a C425S site-directed
mutant. The highly conserved 89 amino acid region from T408 to Q496 is shown to
possess a new fold. The wild-type (WT) structure features two monomers linked by
a Cys425-Cys425 disulfide bond in one asymmetric unit. The monomers are arranged
with their N- and C-termini in opposite orientations to form an "open"
conformation. Mutation of Cys425 to Ser did not affect the monomer structure,
although the mutant dimer adopts strikingly different conformations by crystal
packing, with the cross-linked C-termini and parallel N-termini of two monomers
forming a "closed" conformation. The WT nsp4C exists as a dimer in solution and
can dissociate easily into monomers in a reducing environment.
CONCLUSIONS/SIGNIFICANCE: As nsp4C is exposed in the reducing cytosol, the
monomer of nsp4C should be physiological. This structure may serve as a basis
for further functional studies of nsp4.
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