PDBsum entry 1i1r

Cytokine

PDB id: 1i1r

Contents

Protein chains

301 a.a. *

167 a.a. *

Waters ×370

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Structure of an extracellular gp130 cytokine receptor signaling complex.

Authors

D.Chow, X.He, A.L.Snow, S.Rose-John, K.C.Garcia.

Ref.

Science, 2001, 291, 2150-2155. [DOI no: 10.1126/science.1058308]

PubMed id

11251120

Abstract

The activation of gp130, a shared signal-transducing receptor for a family of cytokines, is initiated by recognition of ligand followed by oligomerization into a higher order signaling complex. Kaposi's sarcoma-associated herpesvirus encodes a functional homolog of human interleukin-6 (IL-6) that activates human gp130. In the 2.4 angstrom crystal structure of the extracellular signaling assembly between viral IL-6 and human gp130, two complexes are cross-linked into a tetramer through direct interactions between the immunoglobulin domain of gp130 and site III of viral IL-6, which is necessary for receptor activation. Unlike human IL-6 (which uses many hydrophilic residues), the viral cytokine largely uses hydrophobic amino acids to contact gp130, which enhances the complementarity of the viral IL-6-gp130 binding interfaces. The cross-reactivity of gp130 is apparently due to a chemical plasticity evident in the amphipathic gp130 cytokine-binding sites.

Figure 1.
Fig. 1. Electron density in the site III interface of the vIL-6-gp130 complex. Viral IL-6 is in yellow and the gp130 D1 domain is in red. At the center of the map is vIL-6 Trp144, which is at the core of the site III interface. The -sheet strands of the gp130 D1 (F and G strands) are labeled in red. The electron density map is a SIGMAA-weighted 2F[obs] - F[calc] map at 2.4 Å contoured at 1.2 and displayed with the program O (45).

Figure 3.
Fig. 3. Molecular anatomy and shape complementarity of the site II interface. (A) Amino acid contact residues within the site II interface; gp130 (blue) is at the left and vIL-6 (purple) at the right, and hydrogen bonds appear as red dotted lines. The conserved gp130 Phe^169 and vIL-6 Trp18 are in the center of the interface. (B and C) The site II vIL-6-gp130 interface is peeled open, and the contact residues of one molecule are projected onto the buried surface (red) of the interacting protein. Trp18 of vIL-6 (green) and Phe^169 of gp130 (blue) are used as anchor points (arrows) to orient the reader between the two surfaces. In (B), the gp130 contact residues (yellow) and binding-site loops (blue) are shown as sticks projected onto the molecular surface of vIL-6, where the buried portion is highlighted in red. A deep canyon that receives the protruding gp130 elbow is evident on the surface of vIL-6. The central Trp18 of vIL-6 is highlighted on the red surface as a green patch. In (C), the vIL-6 contact residues (yellow) and helices (pink) are drawn as sticks projected onto the protruding molecular surface of gp130. The Phe^169 of gp130 is drawn as a blue patch [see (38)].

The above figures are reprinted by permission from the AAAs: Science (2001, 291, 2150-2155) copyright 2001.