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PDBsum entry 4tn3
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Antiviral protein
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PDB id
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4tn3
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References listed in PDB file
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Key reference
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Title
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Structural studies of postentry restriction factors reveal antiparallel dimers that enable avid binding to the HIV-1 capsid lattice.
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Authors
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D.C.Goldstone,
P.A.Walker,
L.J.Calder,
P.J.Coombs,
J.Kirkpatrick,
N.J.Ball,
L.Hilditch,
M.W.Yap,
P.B.Rosenthal,
J.P.Stoye,
I.A.Taylor.
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Ref.
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Proc Natl Acad Sci U S A, 2014,
111,
9609-9614.
[DOI no: ]
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PubMed id
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Abstract
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Restriction factors (RFs) form important components of host defenses to
retroviral infection. The Fv1, Trim5α, and TrimCyp RFs contain N-terminal
dimerization and C-terminal specificity domains that target assembled retroviral
capsid (CA) proteins enclosing the viral core. However, the molecular detail of
the interaction between RFs and their CA targets is unknown. Therefore, we have
determined the crystal structure of the B-box and coiled-coil (BCC) region from
Trim5α and used small-angle X-ray scattering to examine the solution structure
of Trim5α BCC, the dimerization domain of Fv1 (Fv1Ntd), and the hybrid
restriction factor Fv1Cyp comprising Fv1NtD fused to the HIV-1 binding protein
Cyclophilin A (CypA). These data reveal that coiled-coil regions of Fv1 and
Trim5α form extended antiparallel dimers. In Fv1Cyp, two CypA moieties are
located at opposing ends, creating a molecule with a dumbbell appearance. In
Trim5α, the B-boxes are located at either end of the coiled-coil, held in place
by interactions with a helical motif from the L2 region of the opposing monomer.
A comparative analysis of Fv1Cyp and CypA binding to a preformed HIV-1 CA
lattice reveals how RF dimerization enhances the affinity of interaction through
avidity effects. We conclude that the antiparallel organization of the NtD
regions of Fv1 and Trim5α dimers correctly positions C-terminal specificity and
N-terminal effector domains and facilitates stable binding to adjacent CA
hexamers in viral cores.
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