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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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Obsolete entry |
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PDB id:
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| Name: |
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Immune system
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Title:
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Interleukin-23 complex with an antagonistic alphabody, crystal form 1
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Structure:
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Interleukin-12 subunit beta. Chain: a. Synonym: il-12b, cytotoxic lymphocyte maturation factor 40 kda subunit, clmf p40, il-12 subunit p40, nk cell stimulatory factor chain 2, nksf2. Engineered: yes. Interleukin-23 subunit alpha. Chain: b. Synonym: il-23 subunit alpha, il-23-a, interleukin-23 subunit p19,
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Gene: il12b, nksf2. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293t. Gene: il23a, sgrf, unq2498/pro5798. In-silico.
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Resolution:
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1.74Å
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R-factor:
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0.176
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R-free:
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0.215
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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.Hendrikx, I.Lasters,S.N.Savvides
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Key ref:
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J.Desmet
et al.
(2014).
Structural basis of IL-23 antagonism by an Alphabody protein scaffold.
Nat Commun,
5,
5237.
PubMed id:
DOI:
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Date:
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12-Jan-14
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Release date:
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05-Nov-14
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PROCHECK
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Headers
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References
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P29460
(IL12B_HUMAN) -
Interleukin-12 subunit beta from Homo sapiens
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Seq:
Struc:
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328 a.a.
302 a.a.
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DOI no:
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Nat Commun
5:5237
(2014)
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PubMed id:
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Structural basis of IL-23 antagonism by an Alphabody protein scaffold.
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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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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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Links
