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PDBsum entry 3pnw
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Protein binding/immune system
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PDB id
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3pnw
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Contents |
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(+ 2 more)
213 a.a.
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(+ 2 more)
225 a.a.
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60 a.a.
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53 a.a.
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55 a.a.
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* Residue conservation analysis
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PDB id:
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| Name: |
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Protein binding/immune system
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Title:
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Crystal structure of the tudor domain of human tdrd3 in complex with an anti-tdrd3 fab
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Structure:
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Fab light chain. Chain: a, d, g, j, m, p, s, v. Engineered: yes. Fab heavy chain. Chain: b, e, h, k, n, q, t, w. Engineered: yes. Tudor domain-containing protein 3. Chain: c, f, i, l, o, r, u, x. Engineered: yes
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Source:
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Homo sapiens, synthetic construct. Organism_taxid: 9606, 32630. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Human. Organism_taxid: 9606. Gene: tdrd3.
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Resolution:
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2.05Å
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R-factor:
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0.224
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R-free:
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0.264
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Authors:
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P.Loppnau,W.Tempel,A.K.Wernimont,R.Lam,M.Ravichandran,M.A.Adams- Cioaba,H.Persson,S.S.Sidhu,C.H.Arrowsmith,A.M.Edwards,C.Bountra, J.Weigelt,D.Cossar,Structural Genomics Consortium (Sgc)
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Key ref:
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H.Persson
et al.
(2013).
CDR-H3 diversity is not required for antigen recognition by synthetic antibodies.
J Mol Biol,
425,
803-811.
PubMed id:
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Date:
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19-Nov-10
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Release date:
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01-Dec-10
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PROCHECK
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Headers
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References
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No UniProt id for this chain
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No UniProt id for this chain
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Q9H7E2
(TDRD3_HUMAN) -
Tudor domain-containing protein 3 from Homo sapiens
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Seq:
Struc:
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651 a.a.
60 a.a.
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J Mol Biol
425:803-811
(2013)
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PubMed id:
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CDR-H3 diversity is not required for antigen recognition by synthetic antibodies.
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H.Persson,
W.Ye,
A.Wernimont,
J.J.Adams,
A.Koide,
S.Koide,
R.Lam,
S.S.Sidhu.
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ABSTRACT
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A synthetic phage-displayed antibody repertoire was constructed with equivalent
chemical diversity in the third complementarity-determining regions of the heavy
(CDR-H3) and light (CDR-L3) chains, which contrasts with natural antibodies in
which CDR-H3 is much more diverse than CDR-L3 due to the genetic mechanisms that
generate antibody encoding genes. Surprisingly, the synthetic repertoire yielded
numerous functional antibodies that contained mutated CDR-L3 sequences but a
fixed CDR-H3 sequence. Alanine-scanning analysis of antibodies that recognized
10 different antigens but contained a common CDR-H3 loop showed that, in most
cases, the fixed CDR-H3 sequence was able to contribute favorably to antigen
recognition, but in some cases, the loop was functionally inert. Structural
analysis of one such antibody in complex with antigen showed that the inert
CDR-H3 loop was nonetheless highly buried at the antibody-antigen interface.
Taken together, these results show that CDR-H3 diversity is not necessarily
required for the generation of antibodies that recognize diverse protein
antigens with high affinity and specificity, and if given the chance, CDR-L3
readily assumes the dominant role for antigen recognition. These results
contrast with the commonly accepted view of antigen recognition derived from the
analysis of natural antibodies, in which CDR-H3 is presumed to be dominant and
CDR-L3 is presumed to play an auxiliary role. Furthermore, the results show that
natural antibody function is genetically constrained, and it should be possible
to develop more functional synthetic antibody libraries by expanding the
diversity of CDR-L3 beyond what is observed in nature.
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