Structural change and receptor binding in a chemokine mutant with a rearranged disulfide: X-ray structure of e38C/C50A IL-8 at 2 Å resolution
✍ Scribed by Charles Eigenbrot; Henry B. Lowman; Linda Chee; Dean R. Artis
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 163 KB
- Volume
- 27
- Category
- Article
- ISSN
- 0887-3585
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✦ Synopsis
The characteristic CXC chemokine disulfide core of interleukin-8 (IL-8) has been rearranged in a variant replacing the 9-50 disulfide with a 9-38 disulfide. The new variant has been characterized by its binding affinity to IL-8 receptors A and B and the erythrocyte receptor DARC. This variant binds the three receptors with affinities between 500and 2,500-fold lower than wild-type IL-8. Binding affinity results are also reported for the variant with alanine substituted for both cysteines 9 and 50. The Glu38 8 Cys/Cys50 8 Ala IL-8 crystallizes in space group P2 1 2 1 2 1 with cell parameters a 5 46.4, b 5 49.2, and c 5 69.5 Å, and has been refined to an R-value of 19.4% for data from 10 to 2 Å resolution. Analysis of the structure confirms the new disulfide arrangement and suggests that changes at Ile10 may be the principal cause of the lowered affinities.