PDBsum entry 3d85

Immune system/cytokine

PDB id: 3d85

Contents

Protein chains

213 a.a. *

216 a.a. *

133 a.a. *

290 a.a. *

Ligands

IMD

MPD ×2

Waters ×906

* Residue conservation analysis

PDB id:

3d85

Name:

Immune system/cytokine

Title:

Crystal structure of il-23 in complex with neutralizing fab

Structure:

Fab of antibody 7g10, light chain. Chain: a. Fragment: light chain. Fab of antibody 7g10, heavy chain. Chain: b. Fragment: heavy chain. Interleukin-23 subunit p19. Chain: c. Fragment: subunit p19.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: il23a, sgrf, unq2498/pro5798. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: hi-five cells. Gene: il12b, nksf2.

Resolution:

1.90Å R-factor: 0.172 R-free: 0.215

Authors:

B.M.Beyer,R.Ingram,L.Ramanathan,P.Reichert,H.Le,V.Madison

Key ref:

B.M.Beyer et al. (2008). Crystal structures of the pro-inflammatory cytokine interleukin-23 and its complex with a high-affinity neutralizing antibody. J Mol Biol, 382, 942-955. PubMed id: 18708069 DOI: 10.1016/j.jmb.2008.08.001

Date:

22-May-08 Release date: 02-Sep-08

Protein chain

No UniProt id for this chain

Struc: 213 a.a.

Protein chain

P01857  (IGHG1_HUMAN) -  Immunoglobulin heavy constant gamma 1 from Homo sapiens

Seq: 399 a.a.

Struc: 216 a.a.

Protein chain

Q9NPF7  (IL23A_HUMAN) -  Interleukin-23 subunit alpha from Homo sapiens

Seq: 189 a.a.

Struc: 133 a.a.

Protein chain

P29460  (IL12B_HUMAN) -  Interleukin-12 subunit beta from Homo sapiens

Seq: 328 a.a.

Struc: 290 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1016/j.jmb.2008.08.001

J Mol Biol 382:942-955 (2008)

PubMed id: 18708069

Crystal structures of the pro-inflammatory cytokine interleukin-23 and its complex with a high-affinity neutralizing antibody.

B.M.Beyer, R.Ingram, L.Ramanathan, P.Reichert, H.V.Le, V.Madison, P.Orth.

ABSTRACT

Interleukin (IL)-23 is a pro-inflammatory cytokine playing a key role in the pathogenesis of several autoimmune and inflammatory diseases. We have determined the crystal structures of the heterodimeric p19-p40 IL-23 and its complex with the Fab (antigen-binding fragment) of a neutralizing antibody at 2.9 and 1.9 A, respectively. The IL-23 structure closely resembles that of IL-12. They share the common p40 subunit, and IL-23 p19 overlaps well with IL-12 p35. Along the hydrophilic heterodimeric interface, fewer charged residues are involved for IL-23 compared with IL-12. The binding site of the Fab is located exclusively on the p19 subunit, and comparison with published cytokine-receptor structures suggests that it overlaps with the IL-23 receptor binding site.

Selected figure(s)

Figure 6.
Fig. 6. Unfolded C-terminus of p19 helix B is recognized by 7G10. Hydrogen bonds are shown as dotted lines. Tyr54 forms hydrophobic interactions with Gly86.

Figure 10.
Fig. 10. Specific interactions along the p19–7G10 interface. (a) His92^L and p19 residue Trp137 form an aromatic stacking. A larger aromatic residue, such as Trp or Tyr, would improve these interactions. (b) Tyr54^H hydrogen bonds to Glu82 and His106 and forms hydrophobic contact with Gly86. (c) p19 residues Glu93 and Arg139 are buried within the 7G10–p19 interface. The side chain of Phe94^L is 3.8 Å apart from Arg139. Mutating Phe94^L residue into a Tyr would create an additional hydrogen bond. Additionally, modifying Lys59^H into a medium-sized hydrophobic group, such as Ile or Leu, might improve the van der Waals contacts with Phe94^L and Pro133 of p19. (d) Side-chain interactions between Tyr32^L and Tyr50^L and Pro50 as well as Asp101^H and Ser95.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 382, 942-955) copyright 2008.

Figures were selected by the author.