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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
Author(s) -
Eigenbrot Charles,
Lowman Henry B.,
Chee Linda,
Artis Dean R.
Publication year - 1997
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(199704)27:4<556::aid-prot8>3.0.co;2-8
Subject(s) - chemistry , disulfide bond , receptor , stereochemistry , affinities , mutant , b2 receptor , alanine scanning , alanine , chemokine receptor , crystallography , chemokine , biochemistry , mutagenesis , amino acid , gene , bradykinin
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 500‐ and 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 → Cys/Cys50 → Ala IL‐8 crystallizes in space group P2 1 2 1 2 1 with cell parameters a = 46.4, b = 49.2, and c = 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. © 1997 Wiley‐Liss Inc.