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Chemokine‐Glycosaminoglycan Binding: Specificity for CCR‐11 Ligand Binding to Highly Sulfated Oligosaccharides using FTICR MS
Author(s) -
Leary Julie Ann,
Yu Yonghao,
Saad Ola M.,
Sweeney Matthew
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a914
Subject(s) - chemistry , chemokine , glycosaminoglycan , chemokine receptor , eotaxin , biochemistry , sulfation , ligand (biochemistry) , ccl7 , ccl21 , receptor
Chemokine ligands that are specific to the CCR11 receptor include the proteins MCP1, MCP2, MCP3, MCP4 and Eotaxin. These ligands form non‐covalent complexes with specific sulfated saccharides prior to binding to the receptor. Mass Spectrometry has been used to show that when a library of glycosaminoglycans (GAG) octasaccharides is incubated with the various ligands, very specific interactions occur between the chemokine and octasaccharides. Experiments involving the non‐covalent complex between GAG and chemokine show not only saccharide specificity but also isomeric specificity. FTICR mass spectrometry was used to analyze a library of differentially sulfated octasaccharides (GAG's) that was incubated with various chemokine ligands. In the incubation of the octasaccharide library with the chemokine MCP‐1, it was found that those GAG octasaccharides having 10, 11 and 12 sulfates were found to be specific binders to MCP‐1. Additionally, the chemokines were observed to multimerize to dimers and tetramers during the GAG binding process. This data from the non‐covalent complexes supported previous results, which indicated that GAG binding to chemokines initiates a multimerization process of the chemokines. Dimerization of the protein upon specific GAG binding is clearly observed in the mass spectra, but only for some of the CCR11 ligands; i.e. MCP1 and 2 but not 3, 4 or eotaxin. It is believed that this multimerization is critical for chemokine binding to the CCR11 receptor as well as being responsible for subsequent receptor activity.