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Structure‐activity relationships of chemokines
Author(s) -
ClarkLewis Ian,
Kim KeySun,
Rajarathnam Krishnakumar,
Gong JiangHong,
Dewald Beatrice,
Moser Bernhard,
Baggiolini Marco,
Sykes Brian D.
Publication year - 1995
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.57.5.703
Subject(s) - biology , receptor , binding site , chemokine , chemokine receptor , microbiology and biotechnology , biochemistry , biophysics
Abstract Structural analysis of chemokines has revealed that the α/β structural‐fold is highly conserved among both the CXC and CC chemokine classes. Although dimerization and aggregation is often observed, the chemokines function as monomers. The critical receptor binding regions are in the NH 2 ‐terminal 20 residues of the protein and are the least ordered in solution. The flexible NH 2 ‐terminal region is the most critical receptor binding site and a second site also exists in the loop that follows the two disulfides. The well‐ordered regions are not directly involved in receptor binding but, along with the disulfides, they provide a scaffold that determines the conformation of the sites that are critical for receptor binding. These general requirements for function are common to all the chemokines. For the CC chemokines, receptor activation and receptor binding regions are separate within the 10 residue NH 2 ‐terminal region. This has allowed identification of high affinity analogs that do not activate the receptor and are potent antagonists. J. Leukoc. Biol. 57: 703–711; 1995.