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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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DOI no:
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Proc Natl Acad Sci U S A
99:10641-10646
(2002)
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PubMed id:
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The crystal structure of human CD21: Implications for Epstein-Barr virus and C3d binding.
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A.E.Prota,
D.R.Sage,
T.Stehle,
J.D.Fingeroth.
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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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Selected figure(s)
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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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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.M.van den Elsen,
and
D.E.Isenman
(2011).
A crystal structure of the complex between human complement receptor 2 and its ligand C3d.
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Science,
332,
608-611.
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PDB code:
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J.M.Kovacs,
J.P.Hannan,
E.Z.Eisenmesser,
and
V.M.Holers
(2009).
Mapping of the C3d ligand binding site on complement receptor 2 (CR2/CD21) using nuclear magnetic resonance and chemical shift analysis.
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J Biol Chem,
284,
9513-9520.
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S.J.Perkins,
A.I.Okemefuna,
R.Nan,
K.Li,
and
A.Bonner
(2009).
Constrained solution scattering modelling of human antibodies and complement proteins reveals novel biological insights.
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J R Soc Interface,
6,
S679-S696.
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V.Krishnan,
Y.Xu,
K.Macon,
J.E.Volanakis,
and
S.V.Narayana
(2009).
The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation.
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Acta Crystallogr D Biol Crystallogr,
65,
266-274.
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PDB code:
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D.Liu,
J.Y.Zhu,
and
Z.X.Niu
(2008).
Molecular structure and expression of anthropic, ovine, and murine forms of complement receptor type 2.
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Clin Vaccine Immunol,
15,
901-910.
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K.A.Young,
A.P.Herbert,
P.N.Barlow,
V.M.Holers,
and
J.P.Hannan
(2008).
Molecular basis of the interaction between complement receptor type 2 (CR2/CD21) and Epstein-Barr virus glycoprotein gp350.
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J Virol,
82,
11217-11227.
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B.Royer,
D.C.Soares,
P.N.Barlow,
R.E.Bontrop,
P.Roll,
A.Robaglia-Schlupp,
A.Blancher,
A.Levasseur,
P.Cau,
P.Pontarotti,
and
P.Szepetowski
(2007).
Molecular evolution of the human SRPX2 gene that causes brain disorders of the Rolandic and Sylvian speech areas.
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BMC Genet,
8,
72.
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M.Benvenuti,
and
S.Mangani
(2007).
Crystallization of soluble proteins in vapor diffusion for x-ray crystallography.
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Nat Protoc,
2,
1633-1651.
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G.Szakonyi,
M.G.Klein,
J.P.Hannan,
K.A.Young,
R.Z.Ma,
R.Asokan,
V.M.Holers,
and
X.S.Chen
(2006).
Structure of the Epstein-Barr virus major envelope glycoprotein.
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Nat Struct Mol Biol,
13,
996.
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PDB code:
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H.Ding,
W.M.Prodinger,
and
J.Kopecek
(2006).
Two-step fluorescence screening of CD21-binding peptides with one-bead one-compound library and investigation of binding properties of N-(2-hydroxypropyl)methacrylamide copolymer-peptide conjugates.
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Biomacromolecules,
7,
3037-3046.
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L.Zhang,
and
D.Morikis
(2006).
Immunophysical properties and prediction of activities for vaccinia virus complement control protein and smallpox inhibitor of complement enzymes using molecular dynamics and electrostatics.
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Biophys J,
90,
3106-3119.
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L.Aldaz-Carroll,
J.C.Whitbeck,
M.Ponce de Leon,
H.Lou,
L.Hirao,
S.N.Isaacs,
B.Moss,
R.J.Eisenberg,
and
G.H.Cohen
(2005).
Epitope-mapping studies define two major neutralization sites on the vaccinia virus extracellular enveloped virus glycoprotein B5R.
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J Virol,
79,
6260-6271.
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T.Stehle,
and
T.S.Dermody
(2003).
Structural evidence for common functions and ancestry of the reovirus and adenovirus attachment proteins.
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Rev Med Virol,
13,
123-132.
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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Links
