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PDBsum entry 1kac
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Viral protein/receptor
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PDB id
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1kac
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Contents |
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* Residue conservation analysis
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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 analysis of the mechanism of adenovirus binding to its human cellular receptor, Car.
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Authors
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M.C.Bewley,
K.Springer,
Y.B.Zhang,
P.Freimuth,
J.M.Flanagan.
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Ref.
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Science, 1999,
286,
1579-1583.
[DOI no: ]
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PubMed id
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Abstract
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Binding of virus particles to specific host cell surface receptors is known to
be an obligatory step in infection even though the molecular basis for these
interactions is not well characterized. The crystal structure of the adenovirus
fiber knob domain in complex with domain I of its human cellular receptor,
coxsackie and adenovirus receptor (CAR), is presented here. Surface-exposed
loops on knob contact one face of CAR, forming a high-affinity complex. Topology
mismatches between interacting surfaces create interfacial solvent-filled
cavities and channels that may be targets for antiviral drug therapy. The
structure identifies key determinants of binding specificity, which may suggest
ways to modify the tropism of adenovirus-based gene therapy vectors.
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Figure 2.
Fig. 2. A molecular surface representation of the interface in
the Ad12 knob-CAR D1 complex. (A) Sequence conservation surface
diagram of two knob monomers viewed at the CAR interface. The
molecules are colored on a sliding scale from white (conserved)
to red (nonconserved). Conservation analysis was based on an
alignment of all human Ad knob sequences available in GenBank. A
white strip of conservation transects the surface of the
molecule. Upon binding, the CAR D1 molecule occludes the
conserved strip on Ad12 knob. (B) Surface diagram of two
adjacent Ad12 knob monomers shown in the same view as (A). The
molecules are colored on a sliding scale from yellow (contact)
to red (no contact). Atoms in contact with CAR D1 are shared
between monomers. (C) Surface diagram of CAR D1. The molecules
are colored on a sliding scale from magenta (contact) to cyan
(no contact). This figure was generated with GRASP (30).
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Figure 3.
Fig. 3. CPK model of the region around the cavity. The three
consecutive proline residues in Ad12 knob partially shape the
cavity, which is colored magenta. The AB loop, whose carbon
atoms are colored yellow, lines one side of the cavity. The
carbon atoms from the remainder of the monomer are colored red,
those of the second knob monomer, green, and those of CAR D1,
cyan. All oxygen and nitrogen atoms are colored light red and
blue, respectively. The cavity is lined with atoms from residues
 ,
 (backbone),
 (side),
V448 (side),  (backbone),
V450, L455 (side), Q535 (side), P573 (side), and S575 (side)
from one Ad12 knob; S514 (backbone), A515 (backbone),  (side),
N520 (side), A524 (main), E523, K525, and S526 (side) from the
other Ad12 knob; and L39 (side), K47 (backbone), V48 (backbone),
D49, Q50, V51, and K102 (side) from CAR. The underlined residues
are conserved or similar in all CAR-binding Ad serotypes.
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The above figures are
reprinted
by permission from the AAAs:
Science
(1999,
286,
1579-1583)
copyright 1999.
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