PDBsum entry 3l5y

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protein Protein-protein interface(s) links
Immune system PDB id
Protein chains
213 a.a. *
224 a.a. *
85 a.a. *
* Residue conservation analysis
Superseded by: 4ps4
PDB id:
Name: Immune system
Title: Crystal structure of the complex between il-13 and m1295 fab
Structure: M1295 light chain. Chain: l. Engineered: yes. M1295 heavy chain. Chain: h. Engineered: yes. Interleukin-13. Chain: a. Fragment: unp residues 35-146.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek cells. Gene: il13, nc30. Expressed in: escherichia coli. Expression_system_taxid: 562
2.80Å     R-factor:   0.214     R-free:   0.265
Authors: A.Teplyakov,G.Obmolova,T.Malia,G.L.Gilliland
Key ref: J.Fransson et al. (2010). Human framework adaptation of a mouse anti-human IL-13 antibody. J Mol Biol, 398, 214-231. PubMed id: 20226193 DOI: 10.1016/j.jmb.2010.03.004
22-Dec-09     Release date:   14-Apr-10    
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Protein chain
No UniProt id for this chain
Struc: 213 a.a.
Protein chain
No UniProt id for this chain
Struc: 224 a.a.
Protein chain
Pfam   ArchSchema ?
P35225  (IL13_HUMAN) -  Interleukin-13
146 a.a.
85 a.a.
Key:    PfamA domain  Secondary structure  CATH domain


DOI no: 10.1016/j.jmb.2010.03.004 J Mol Biol 398:214-231 (2010)
PubMed id: 20226193  
Human framework adaptation of a mouse anti-human IL-13 antibody.
J.Fransson, A.Teplyakov, G.Raghunathan, E.Chi, W.Cordier, T.Dinh, Y.Feng, J.Giles-Komar, G.Gilliland, B.Lollo, T.J.Malia, W.Nishioka, G.Obmolova, S.Zhao, Y.Zhao, R.V.Swanson, J.C.Almagro.
Humanization of a potent neutralizing mouse anti-human IL-13 antibody (m836) using a method called human framework adaptation (HFA) is reported. HFA consists of two steps: human framework selection (HFS) and specificity-determining residue optimization (SDRO). The HFS step involved generation of a library of m836 antigen binding sites combined with diverse human germline framework regions (FRs), which were selected based on structural and sequence similarities between mouse variable domains and a repertoire of human antibody germline genes. SDRO consisted of diversifying specificity-determining residues and selecting variants with improved affinity using phage display. HFS of m836 resulted in a 5-fold loss of affinity, whereas SDRO increased the affinity up to 100-fold compared to the HFS antibody. Crystal structures of Fabs in complex with IL-13 were obtained for m836, the HFS variant chosen for SDRO, and one of the highest-affinity SDRO variants. Analysis of the structures revealed that major conformational changes in FR-H1 and FR-H3 occurred after FR replacement, but none of them had an evident direct impact on residues in contact with IL-13. Instead, subtle changes affected the V(L)/V(H) (variable-light domain/variable-heavy domain) interface and were likely responsible for the 5-fold decreased affinity. After SDRO, increased affinity resulted mainly from rearrangements in hydrogen-bonding pattern at the antibody/antigen interface. Comparison with m836 putative germline genes suggested interesting analogies between natural affinity maturation and the engineering process that led to the potent HFA anti-human IL-13 antibody.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20693692 G.Obmolova, T.J.Malia, A.Teplyakov, R.Sweet, and G.L.Gilliland (2010).
Promoting crystallization of antibody-antigen complexes via microseed matrix screening.
  Acta Crystallogr D Biol Crystallogr, 66, 927-933.  
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