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PDBsum entry 1a8o
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Viral protein
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PDB id
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1a8o
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References listed in PDB file
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Key reference
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Title
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Structure of the carboxyl-Terminal dimerization domain of the HIV-1 capsid protein.
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Authors
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T.R.Gamble,
S.Yoo,
F.F.Vajdos,
U.K.Von schwedler,
D.K.Worthylake,
H.Wang,
J.P.Mccutcheon,
W.I.Sundquist,
C.P.Hill.
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Ref.
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Science, 1997,
278,
849-853.
[DOI no: ]
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PubMed id
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Abstract
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The carboxyl-terminal domain, residues 146 to 231, of the human immunodeficiency
virus-1 (HIV-1) capsid protein [CA(146-231)] is required for capsid dimerization
and viral assembly. This domain contains a stretch of 20 residues, called the
major homology region (MHR), which is conserved across retroviruses and is
essential for viral assembly, maturation, and infectivity. The crystal
structures of CA(146-231) and CA(151-231) reveal that the globular domain is
composed of four helices and an extended amino-terminal strand. CA(146-231)
dimerizes through parallel packing of helix 2 across a dyad. The MHR is distinct
from the dimer interface and instead forms an intricate hydrogen-bonding network
that interconnects strand 1 and helices 1 and 2. Alignment of the CA(146-231)
dimer with the crystal structure of the capsid amino-terminal domain provides a
model for the intact protein and extends models for assembly of the central
conical core of HIV-1.
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Figure 3.
Fig. 3. Representative sedimentation profiles of (A) intact
CA, (B) CA(146-231), and (C) CA(M185A) mutant protein. The
analysis reveals that intact CA and CA(146-231) dimerize with
similar affinities (K[d] = 18 ± 1 and 10 ± 3
µM, respectively), but that the CA(M185A) mutation
abolishes dimerization. Theoretical curves for monomer (M) and
monomer/dimer (M/D) distributions are^ shown assuming K[d] = 18
µM (A and C) or 10 µM (B). A[280], absorbance^ at
280 nm.
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Figure 5.
Fig. 5. Model for the intact HIV-1 capsid dimer. The
CA(146-231) dimer (cyan) is shown covalently linked to the
CA(1-151) domain (23). The five disordered residues that connect
the two domains can be modeled to allow ~90° range of
relative rotational orientation for the two domains about the
vertical twofold axis.
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The above figures are
reprinted
by permission from the AAAs:
Science
(1997,
278,
849-853)
copyright 1997.
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