PDBsum entry 1iar

Cytokine/receptor

PDB id: 1iar

Contents

Protein chains

129 a.a. *

188 a.a. *

Waters ×230

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface.

Authors

T.Hage, W.Sebald, P.Reinemer.

Ref.

Cell, 1999, 97, 271-281. [DOI no: 10.1016/S0092-8674(00)80736-9]

PubMed id

10219247

Abstract

Interleukin-4 (IL-4) is a principal regulatory cytokine during an immune response and a crucial determinant for allergy and asthma. IL-4 binds with high affinity and specificity to the ectodomain of the IL-4 receptor alpha chain (IL4-BP). Subsequently, this intermediate complex recruits the common gamma chain (gamma c), thereby initiating transmembrane signaling. The crystal structure of the intermediate complex between human IL-4 and IL4-BP was determined at 2.3 A resolution. It reveals a novel spatial orientation of the two proteins, a small but unexpected conformational change in the receptor-bound IL-4, and an interface with three separate clusters of trans-interacting residues. Novel insights on ligand binding in the cytokine receptor family and a paradigm for receptors of IL-2, IL-7, IL-9, and IL-15, which all utilize gamma c, are provided.

Figure 2.
Figure 2. Structure of Receptor-Bound IL-4Ribbon representation illustrating conformational differences between free IL-4 (yellow, 1rcb [[55]; green, 1int [ [52]) and IL-4 in complex with IL4-BP (red, wild-type IL-4; blue, SeMet-IL-4).

Figure 4.

The above figures are reprinted by permission from Cell Press: Cell (1999, 97, 271-281) copyright 1999.

Secondary reference #1

Title

Crystals of a 1:1 complex between human interleukin-4 and the extracellular domain of its receptor alpha chain.

Authors

T.Hage, P.Reinemer, W.Sebald.

Ref.

Eur J Biochem, 1998, 258, 831-836. [DOI no: 10.1046/j.1432-1327.1998.2580831.x]

PubMed id

9874253

Figure 2.
Fig. 2. Separation of excess free IL­4 from the preformed complex with IL­4BP and SDS­PAGE analysis of chromatographed fractions. (A) Preparative gel filtration chromatography of IL­4 and IL­4 :IL­4BP complex. The IL­4 (600 µM) and IL­4BP (500 µM) were mixed in a 1.2 :1 stoichiometry and equilibrated for 30 min at 4°C. The sample (400 µl) was applied to a Sephacryl S­200 column (Pharmacia) and eluted with the same buffer at 10 ml/h. The elution profile of IL­4 is shown as a control, indicating that excess free ligand upon complex formation can be removed. (B) Coomassie­stained gel (12%) run under non­reducing conditions.

Figure 5.
Fig. 5. Binding of Se­IL­4tetraMet to IL­4BP. Association and dissoci­ ation of the selenomethionine­labelled IL­4 variant was measured by the BIAcore technique using biosensor immobilised IL­4BP. Binding of IL­4 is shown as a control.

The above figures are reproduced from the cited reference with permission from the Federation of European Biochemical Societies