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PDBsum entry 2j12
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Viral protein/receptor
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PDB id
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2j12
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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 and mutational analysis of human ad37 and canine adenovirus 2 fiber heads in complex with the d1 domain of coxsackie and adenovirus receptor.
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Authors
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E.Seiradake,
H.Lortat-Jacob,
O.Billet,
E.J.Kremer,
S.Cusack.
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Ref.
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J Biol Chem, 2006,
281,
33704-33716.
[DOI no: ]
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PubMed id
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Abstract
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Adenovirus fibers from most serotypes bind the D1 domain of coxsackie and
adenovirus receptor (CAR), although the binding residues are not strictly
conserved. To understand this further, we determined the crystal structures of
canine adenovirus serotype 2 (CAV-2) and the human adenovirus serotype 37
(HAd37) in complex with human CAR D1 at 2.3 and 1.5A resolution, respectively.
Structure comparison with the HAd12 fiber head-CAR D1 complex showed that the
overall topology of the interaction is conserved but that the interfaces differ
in number and identity of interacting residues, shape complementarity, and
degree of conformational adaptation. Using surface plasmon resonance, we
characterized the binding affinity to CAR D1 of wild type and mutant CAV-2 and
HAd37 fiber heads. We found that CAV-2 has the highest affinity but fewest
direct interactions, with the reverse being true for HAd37. Moreover, we found
that conserved interactions can have a minor contribution, whereas
serotype-specific interactions can be essential. These results are discussed in
the light of virus evolution and design of adenovirus vectors for gene transfer.
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Figure 2.
FIGURE 2. Cartoon representations of adenovirus fiber heads
in complex with CAR D1. HAd12, HAd37, and CAV-2 fiber heads are
colored blue, pink, and yellow, respectively. CAR D1 is in
green. A, top view of the structure of HAd12 fiber head in
complex with CAR D1 (13). B, as A, but HAd37 fiber head. C, as A
and B, but CAV-2 fiber head. D, part of the binding interface
between HAd12 fiber head and CAR D1 showing some key interacting
residues. E, equivalent region of interface between HAd37 fiber
head and CAR D1 showing conservation of the interactions and
additional unique interactions provided by HAd37 Glu^351 from
the IJ loop. F, same region of the CAV-2 fiber head and CAR D1
interface showing equivalent interactions made by sometimes
different fiber residues. Hydrogen bonds are shown in dotted
lines. Residues marked with an asterisk are not fully
represented for clarity.
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Figure 6.
FIGURE 6. SPR sensorgrams of wild type and mutant
adenovirus fiber heads binding to immobilized CAR D1. A, wild
type HAd37 fiber head; B, HAd37 fiber head mutant S299A; C,
HAd37 fiber head mutant E351A; D, wild type CAV-2 fiber head; E,
CAV-2 fiber head mutant T441A; F, CAV-2 fiber head mutant R384E;
G, CAV-2 fiber head mutant R515A; H, CAV-2 fiber head mutant
G370D; I, CAV-2 fiber head mutant R384A.  , results calculated
from the sensorgrams. The S.E. did not exceed 15% of the K[d].
 ,
Lortat-Jacob et al. (51) using the same experimental set-up and
CAR construct as in this work.  , Kirby et al. (67)
using a longer CAR construct.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2006,
281,
33704-33716)
copyright 2006.
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