Format

Send to

Choose Destination
EMBO J. 1997 Mar 3;16(5):989-97.

1.9 A crystal structure of interleukin 6: implications for a novel mode of receptor dimerization and signaling.

Author information

1
Small Molecule Drug Discovery, Genetics Institute, Inc., Cambridge, MA 02140, USA.

Abstract

Interleukin 6 (IL-6) has many biological activities in vivo, and deregulation has been implicated in many disease processes. IL-6, a 185 amino acid polypeptide was refolded, purified and crystallized. The crystals diffracted to beyond 1.9 A and the structure was solved using single isomorphous replacement. The X-ray structure of IL-6 is composed of a four helix bundle linked by loops and an additional mini-helix. 157 out of 185 residues are well defined in the final structure, with 18 N-terminal and 8 A-B loop amino acids displaying no interpretable electron density. The three-dimensional structure has been used to construct a model of IL-6 interacting with the IL-6 receptor (alpha-chain) and gp130 (beta-chain) that gives new insight into the process of molecular recognition and signaling. Based on this model, we predict a fourth binding site on IL-6, a low affinity IL-6-IL-6 interaction, which may be necessary for the sequential assembly of a functional hexameric IL-6 receptor complex.

PMID:
9118960
PMCID:
PMC1169699
DOI:
10.1093/emboj/16.5.989
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center