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PDBsum entry 2agj
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Immune system
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PDB id
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2agj
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References listed in PDB file
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Key reference
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Title
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Crystal structure of a glycosylated FAB from an igm cryoglobulin with properties of a natural proteolytic antibody.
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Authors
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P.A.Ramsland,
S.S.Terzyan,
G.Cloud,
C.R.Bourne,
W.Farrugia,
G.Tribbick,
H.M.Geysen,
C.R.Moomaw,
C.A.Slaughter,
A.B.Edmundson.
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Ref.
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Biochem J, 2006,
395,
473-481.
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PubMed id
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Abstract
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The 2.6 A (1 A=0.1 nm) resolution structure has been determined for the
glycosylated Fab (fragment antigen binding) of an IgM (Yvo) obtained from a
subject with Waldenström's macroglobulinaemia. Dynamic light scattering was
used to estimate the gel point and monitor the formation of an ordered
hydroscopic gel of Yvo IgM upon cooling. If a cryoglobulin forms gels in
peripheral tissues and organs, the associated swelling and damage to
microvasculature can result in considerable morbidity and mortality. The
three-dimensional structure of the branched N-linked oligosaccharide associated
with the CH1 domain (first constant domain of heavy chain) is reported. The
carbohydrate may act to shield part of the lateral surface of the CH1 domain and
crowd the junction between the CH1 and CH2 domains, thereby limiting the
segmental flexibility of the Fab arms in intact Yvo IgM, especially at low
temperatures. Recently, Yvo IgM was shown to have the properties of a naturally
occurring proteolytic antibody [Paul, Karle, Planque, Taguchi, Salas, Nishiyama,
Handy, Hunter, Edmundson and Hanson (2004) J. Biol. Chem. 279, 39611-39619;
Planque, Bangale, Song, Karle, Taguchi, Poindexter, Bick, Edmundson, Nishiyama
and Paul (2004) J. Biol Chem. 279, 14024-14032]. The Yvo protein displayed the
ability to cleave, by a nucleophilic mechanism, the amide bonds of a variety of
serine protease substrates and the gp120 coat protein of HIV. An atypical
serine, arginine and glutamate motif is located in the middle of the Yvo
antigen-binding site and displays an overall geometry that mimics the classical
serine, histidine and aspartate catalytic triad of serine proteases. Our present
findings indicate that pre-existing or natural antibodies can utilize at least
one novel strategy for the cleavage of peptide bonds.
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Secondary reference #1
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Title
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Interconversion of different crystal forms of fabs from human igm cryoglobulins
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Authors
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P.A.Ramsland,
J.L.Upshaw,
B.B.Shultz,
C.R.Dewitt,
W.F.Chissoe III,
R.L.Raison,
A.B.Edmundson.
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Ref.
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j cryst growth, 2001,
232,
204.
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Secondary reference #2
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Title
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Dealing with intractable protein cores: protein sequencing of the mcg igg and the yvo igm heavy chain variable domains.
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Authors
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D.C.Shaw,
B.B.Shultz,
P.A.Ramsland,
A.B.Edmundson.
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Ref.
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J Mol Recognit, 2002,
15,
341-348.
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PubMed id
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