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PDBsum entry 4k3e
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Immune system
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PDB id
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4k3e
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References listed in PDB file
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Key reference
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Title
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Reshaping antibody diversity.
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Authors
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F.Wang,
D.C.Ekiert,
I.Ahmad,
W.Yu,
Y.Zhang,
O.Bazirgan,
A.Torkamani,
T.Raudsepp,
W.Mwangi,
M.F.Criscitiello,
I.A.Wilson,
P.G.Schultz,
V.V.Smider.
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Ref.
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Cell, 2013,
153,
1379-1393.
[DOI no: ]
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PubMed id
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Abstract
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Some species mount a robust antibody response despite having limited
genome-encoded combinatorial diversity potential. Cows are unusual in having
exceptionally long CDR H3 loops and few V regions, but the mechanism for
creating diversity is not understood. Deep sequencing reveals that ultralong CDR
H3s contain a remarkable complexity of cysteines, suggesting that
disulfide-bonded minidomains may arise during repertoire development. Indeed,
crystal structures of two cow antibodies reveal that these CDR H3s form a very
unusual architecture composed of a β strand "stalk" that supports a
structurally diverse, disulfide-bonded "knob" domain. Diversity arises
from somatic hypermutation of an ultralong DH with a severe codon bias toward
mutation to cysteine. These unusual antibodies can be elicited to recognize
defined antigens through the knob domain. Thus, the bovine immune system
produces an antibody repertoire composed of ultralong CDR H3s that fold into a
diversity of minidomains generated through combinations of somatically generated
disulfides.
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