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PDBsum entry 1ly2
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Immune system
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PDB id
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1ly2
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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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The crystal structure of human cd21: implications for epstein-Barr virus and c3d binding.
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Authors
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A.E.Prota,
D.R.Sage,
T.Stehle,
J.D.Fingeroth.
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Ref.
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Proc Natl Acad Sci U S A, 2002,
99,
10641-10646.
[DOI no: ]
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PubMed id
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Abstract
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Human complement receptor type 2 (CD21) is the cellular receptor for
Epstein-Barr virus (EBV), a human tumor virus. The N-terminal two short
consensus repeats (SCR1-SCR2) of the receptor interact with the EBV glycoprotein
gp350/220 and also with the natural CD21 ligand C3d. Here we present the crystal
structure of the CD21 SCR1-SCR2 fragment in the absence of ligand and
demonstrate that it is able to bind EBV. Based on a functional analysis of
wild-type and mutant CD21 and molecular modeling, we identify a likely region
for EBV attachment and demonstrate that this region is not involved in the
interaction with C3d. A comparison with the previously determined structure of
CD21 SCR1-SCR2 in complex with C3d shows that, in both cases, CD21 assumes
compact V-shaped conformations. However, our analysis reveals a surprising
degree of flexibility at the SCR1-SCR2 interface, suggesting interactions
between the two domains are not specific. We present evidence that the V-shaped
conformation is induced by deglycosylation of the protein, and that physiologic
glycosylation of CD21 would result in a more extended conformation, perhaps with
additional epitopes for C3d binding.
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Figure 2.
Fig 2. Structure and conformation of CD21 SCR1-SCR2. (A)
Ribbon drawing of the crystallized protein, with  -strands
labeled. Disulfide bonds and NAG residues are shown in yellow
and orange, respectively. (B) Interface between domains SCR1 and
SCR2. Amino acids (single-letter code) that participate in the
contact are shown in green. Hydrogen bonds and salt bridges are
represented with dashed lines. A comparison with the structure
of liganded CD21 SCR1-SCR2 (gray) (17) reveals substantial
interdomain flexibility despite extensive interface contacts.
(C) Final 2 F[obs] - F[calc] electron density map at 1.8-Å
resolution, contoured at 0.7  , and centered at NAG107.
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Figure 4.
Fig 4. Changes in CD21 structure upon interaction with its
ligand C3d. (A) Superposition of nonliganded CD21 SCR1-SCR2
(orange) with the CD21 SCR1-SCR2-C3d complex (gray) (17).
Binding of C3d introduces a main-chain shift in the B-B' loop of
SCR2, displacing Ser-85 and unlocking the Arg-83 side chain. The
interaction primarily involves the base of C3d helix H5. The
C3d/CD21 interface contains a nonphysiologic zinc ion (cyan),
which may distort the interaction between CD21 and C3d somewhat
because the zinc-coordinating C3d residue Glu-117 might
otherwise be available to form a salt bridge with Arg-83 or
interact with other CD21 residues. W denotes water molecules.
(B) Differences in interdomain orientation between the
unliganded (orange) and liganded (gray) forms of CD21. The view
is the same as in A; the tracing for C3d has been omitted for
clarity. The small changes at the C3d binding site lead to a
different interdomain orientation. Hydrogen bonds are indicated
with dashed lines. Arrows indicate the directions of main-chain
movements.
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