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PDBsum entry 4oe8
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Immune system
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PDB id
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4oe8
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Contents |
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302 a.a.
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154 a.a.
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87 a.a.
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References listed in PDB file
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Key reference
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Title
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Structural basis of il-23 antagonism by an alphabody protein scaffold.
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Authors
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J.Desmet,
K.Verstraete,
Y.Bloch,
E.Lorent,
Y.Wen,
B.Devreese,
K.Vandenbroucke,
S.Loverix,
T.Hettmann,
S.Deroo,
K.Somers,
P.Henderikx,
I.Lasters,
S.N.Savvides.
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Ref.
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Nat Commun, 2014,
5,
5237.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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Protein scaffolds can provide a promising alternative to antibodies for various
biomedical and biotechnological applications, including therapeutics. Here we
describe the design and development of the Alphabody, a protein scaffold
featuring a single-chain antiparallel triple-helix coiled-coil fold. We report
affinity-matured Alphabodies with favourable physicochemical properties that can
specifically neutralize human interleukin (IL)-23, a pivotal therapeutic target
in autoimmune inflammatory diseases such as psoriasis and multiple sclerosis.
The crystal structure of human IL-23 in complex with an affinity-matured
Alphabody reveals how the variable interhelical groove of the scaffold uniquely
targets a large epitope on the p19 subunit of IL-23 to harness fully the
hydrophobic and hydrogen-bonding potential of tryptophan and tyrosine residues
contributed by p19 and the Alphabody, respectively. Thus, Alphabodies are
suitable for targeting protein-protein interfaces of therapeutic importance and
can be tailored to interrogate desired design and binding-mode principles via
efficient selection and affinity-maturation strategies.
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