Structure-activity relationships of chemokines

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 NH2‐terminal 20...

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Bibliographic Details
Published in:Journal of leukocyte biology 1995-05, Vol.57 (5), p.703-711
Main Authors: Clark‐Lewis, Ian, Kim, Key‐Sun, Rajarathnam, Krishnakumar, Gong, Jiang‐Hong, Dewald, Beatrice, Moser, Bernhard, Baggiolini, Marco, Sykes, Brian D.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Chemokine CCL2
Chemokine CCL7
Chemokine CCL8
Chemokine CXCL1
Chemokines, CXC
Chemotactic Factors - chemistry
Chemotactic Factors - physiology
Cytokines
Disulfides - chemistry
Growth Substances - chemistry
Growth Substances - physiology
Humans
inflammation
Intercellular Signaling Peptides and Proteins
Interleukin-8 - chemistry
Interleukin-8 - physiology
interleukin‐8
Ligands
Molecular Sequence Data
monocyte chemoattractant protein
Monocyte Chemoattractant Proteins
peptide synthesis
Protein Binding
protein engineering
Protein Structure, Tertiary
Receptors, Growth Factor - physiology
Sequence Alignment
Sequence Homology, Amino Acid
Structure-Activity Relationship
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Summary: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 NH2‐terminal 20 residues of the protein and are the least ordered in solution. The flexible NH2‐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 NH2‐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.
ISSN:0741-5400
1938-3673
DOI:10.1002/jlb.57.5.703