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* Residue conservation analysis
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PDB id:
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Immune system
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Title:
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S45-18 fab pentasaccharide bisphosphate complex
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Structure:
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S45-18 fab (igg1k) light chain. Chain: a, c. Fragment: fab1 light chain kappa. S45-18 fab (igg1k) heavy chain. Chain: b, d. Fragment: fab1 heavy chain g1
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Source:
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Mus musculus. House mouse. Organism_taxid: 10090. Organism_taxid: 10090
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Biol. unit:
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Dimer (from
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Resolution:
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1.75Å
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R-factor:
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0.212
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R-free:
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0.247
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Authors:
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H.P.Nguyen,N.O.Seto,C.R.Mackenzie,L.Brade,P.Kosma,H.Brade,S.V.Evans
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Key ref:
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H.P.Nguyen
et al.
(2003).
Germline antibody recognition of distinct carbohydrate epitopes.
Nat Struct Biol,
10,
1019-1025.
PubMed id:
DOI:
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Date:
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26-Aug-03
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Release date:
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27-Jan-04
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PROCHECK
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Headers
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References
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DOI no:
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Nat Struct Biol
10:1019-1025
(2003)
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PubMed id:
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Germline antibody recognition of distinct carbohydrate epitopes.
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H.P.Nguyen,
N.O.Seto,
C.R.MacKenzie,
L.Brade,
P.Kosma,
H.Brade,
S.V.Evans.
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ABSTRACT
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High-resolution structures reveal how a germline antibody can recognize a range
of clinically relevant carbohydrate epitopes. The germline response to a
carbohydrate immunogen can be critical to survivability, with selection for
antibody gene segments that both confer protection against common pathogens and
retain the flexibility to adapt to new disease organisms. We show here that
antibody S25-2 binds several distinct inner-core epitopes of bacterial
lipopolysaccharides (LPSs) by linking an inherited monosaccharide residue
binding site with a subset of complementarity-determining regions (CDRs) of
limited flexibility positioned to recognize the remainder of an array of
different epitopes. This strategy allows germline antibodies to adapt to
different epitopes while minimizing entropic penalties associated with the
immobilization of labile CDRs upon binding of antigen, and provides insight into
the link between the genetic origin of individual CDRs and their respective
roles in antigen recognition.
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Selected figure(s)
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Figure 3.
Figure 3. Binding environments for representative liganded
antigens. The  (2
 arrow
8)- (2
arrow
4) trisaccharide bound to S25-2 is yellow, the (2
arrow
4) disaccharide bound to S25-2 is magenta and the (2
arrow
4)- (2
arrow
4) trisaccharide of the pentasaccharide antigen bound to S45-18
is green. (a) All complexes share a related terminal Kdo binding
pocket. (b) S25-2 shows flexibility in binding the remaining Kdo
residues in range of distinct epitopes, whereas S45-18 uses a
different CDR H3 to specifically recognize one antigen.
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Figure 4.
Figure 4. Conformational variation observed among liganded and
unliganded forms of S25-2 and S45-18. (a) Overlap of
unliganded S25-2 (crystal form 1, dark blue; crystal form 2,
white), S25-2 bound to (2
arrow
8)- (2
arrow
4) trisaccharide (yellow), S25-2 bound to (2
arrow
4) disaccharide (magenta) and S25-2 bound to the Kdo
monosaccharide (cyan). The trace of the (2
arrow
8) disaccharide complex is similar to the (2
arrow
8)- (2
arrow
4) trisaccharide complex and is not shown. (b) Overlap of
unliganded (white) and liganded (green) S45-18.
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The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2003,
10,
1019-1025)
copyright 2003.
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Figures were
selected
by the author.
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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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S.E.Wong,
B.D.Sellers,
and
M.P.Jacobson
(2011).
Effects of somatic mutations on CDR loop flexibility during affinity maturation.
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Proteins,
79,
821-829.
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C.L.Brooks,
R.J.Blackler,
G.Sixta,
P.Kosma,
S.Müller-Loennies,
L.Brade,
T.Hirama,
C.R.MacKenzie,
H.Brade,
and
S.V.Evans
(2010).
The role of CDR H3 in antibody recognition of a synthetic analog of a lipopolysaccharide antigen.
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Glycobiology,
20,
138-147.
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PDB codes:
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H.Mao,
J.J.Graziano,
T.M.Chase,
C.A.Bentley,
O.A.Bazirgan,
N.P.Reddy,
B.D.Song,
and
V.V.Smider
(2010).
Spatially addressed combinatorial protein libraries for recombinant antibody discovery and optimization.
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Nat Biotechnol,
28,
1195-1202.
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S.Gerstenbruch,
C.L.Brooks,
P.Kosma,
L.Brade,
C.R.Mackenzie,
S.V.Evans,
H.Brade,
and
S.Müller-Loennies
(2010).
Analysis of cross-reactive and specific anti-carbohydrate antibodies against lipopolysaccharide from Chlamydophila psittaci.
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Glycobiology,
20,
461-472.
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C.H.Liang,
and
C.Y.Wu
(2009).
Glycan array: a powerful tool for glycomics studies.
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Expert Rev Proteomics,
6,
631-645.
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P.A.Christensen,
A.Danielczyk,
P.Ravn,
M.Larsen,
R.Stahn,
U.Karsten,
and
S.Goletz
(2009).
Modifying antibody specificity by chain shuffling of V / V between antibodies with related specificities.
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Scand J Immunol,
69,
1.
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T.Biswas,
L.Yi,
P.Aggarwal,
J.Wu,
J.R.Rubin,
J.A.Stuckey,
R.W.Woodard,
and
O.V.Tsodikov
(2009).
The tail of KdsC: conformational changes control the activity of a haloacid dehalogenase superfamily phosphatase.
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J Biol Chem,
284,
30594-30603.
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PDB codes:
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C.L.Brooks,
R.J.Blackler,
S.Gerstenbruch,
P.Kosma,
S.Müller-Loennies,
H.Brade,
and
S.V.Evans
(2008).
Pseudo-symmetry and twinning in crystals of homologous antibody Fv fragments.
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Acta Crystallogr D Biol Crystallogr,
64,
1250-1258.
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PDB codes:
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D.Kuroda,
H.Shirai,
M.Kobori,
and
H.Nakamura
(2008).
Structural classification of CDR-H3 revisited: a lesson in antibody modeling.
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Proteins,
73,
608-620.
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F.Ahmed,
G.André-Leroux,
A.Haouz,
A.Boutonnier,
M.Delepierre,
F.Qadri,
F.Nato,
J.M.Fournier,
and
P.M.Alzari
(2008).
Crystal structure of a monoclonal antibody directed against an antigenic determinant common to Ogawa and Inaba serotypes of Vibrio cholerae O1.
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Proteins,
70,
284-288.
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PDB code:
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K.Kiernan,
I.Harnden,
M.Gunthart,
C.Gregory,
J.Meisner,
and
M.Kearns-Jonker
(2008).
The anti-non-gal xenoantibody response to xenoantigens on gal knockout pig cells is encoded by a restricted number of germline progenitors.
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Am J Transplant,
8,
1829-1839.
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L.Krishnan,
G.Sahni,
K.J.Kaur,
and
D.M.Salunke
(2008).
Role of antibody paratope conformational flexibility in the manifestation of molecular mimicry.
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Biophys J,
94,
1367-1376.
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PDB code:
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F.W.Peyerl,
S.Dai,
G.A.Murphy,
F.Crawford,
J.White,
P.Marrack,
and
J.W.Kappler
(2007).
Elucidation of some Bax conformational changes through crystallization of an antibody-peptide complex.
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Cell Death Differ,
14,
447-452.
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PDB code:
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J.D.Dimitrov,
L.T.Roumenina,
V.R.Doltchinkova,
N.M.Mihaylova,
S.Lacroix-Desmazes,
S.V.Kaveri,
and
T.L.Vassilev
(2007).
Antibodies use heme as a cofactor to extend their pathogen elimination activity and to acquire new effector functions.
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J Biol Chem,
282,
26696-26706.
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J.Milland,
E.Yuriev,
P.X.Xing,
I.F.McKenzie,
P.A.Ramsland,
and
M.S.Sandrin
(2007).
Carbohydrate residues downstream of the terminal Galalpha(1,3)Gal epitope modulate the specificity of xenoreactive antibodies.
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Immunol Cell Biol,
85,
623-632.
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M.Kearns-Jonker,
N.Barteneva,
R.Mencel,
N.Hussain,
I.Shulkin,
A.Xu,
M.Yew,
and
D.V.Cramer
(2007).
Use of molecular modeling and site-directed mutagenesis to define the structural basis for the immune response to carbohydrate xenoantigens.
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BMC Immunol,
8,
3.
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P.Scheerer,
A.Kramer,
L.Otte,
M.Seifert,
H.Wessner,
C.Scholz,
N.Krauss,
J.Schneider-Mergener,
and
W.Höhne
(2007).
Structure of an anti-cholera toxin antibody Fab in complex with an epitope-derived D-peptide: a case of polyspecific recognition.
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J Mol Recognit,
20,
263-274.
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PDB code:
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D.K.Sethi,
A.Agarwal,
V.Manivel,
K.V.Rao,
and
D.M.Salunke
(2006).
Differential epitope positioning within the germline antibody paratope enhances promiscuity in the primary immune response.
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Immunity,
24,
429-438.
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J.D.Dimitrov,
N.D.Ivanovska,
S.Lacroix-Desmazes,
V.R.Doltchinkova,
S.V.Kaveri,
and
T.L.Vassilev
(2006).
Ferrous ions and reactive oxygen species increase antigen-binding and anti-inflammatory activities of immunoglobulin G.
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J Biol Chem,
281,
439-446.
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E.Altman,
B.A.Harrison,
T.Hirama,
V.Chandan,
R.To,
and
R.MacKenzie
(2005).
Characterization of murine monoclonal antibodies against Helicobacter pylori lipopolysaccharide specific for Lex and Ley blood group determinants.
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Biochem Cell Biol,
83,
589-596.
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C.C.Huang,
M.Venturi,
S.Majeed,
M.J.Moore,
S.Phogat,
M.Y.Zhang,
D.S.Dimitrov,
W.A.Hendrickson,
J.Robinson,
J.Sodroski,
R.Wyatt,
H.Choe,
M.Farzan,
and
P.D.Kwong
(2004).
Structural basis of tyrosine sulfation and VH-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120.
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Proc Natl Acad Sci U S A,
101,
2706-2711.
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PDB codes:
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R.W.Maitta,
K.Datta,
Q.Chang,
R.X.Luo,
B.Witover,
K.Subramaniam,
and
L.A.Pirofski
(2004).
Protective and nonprotective human immunoglobulin M monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan manifest different specificities and gene use profiles.
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Infect Immun,
72,
4810-4818.
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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
codes are
shown on the right.
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Links
