CXCL1/MGSA Is a Novel Glycosaminoglycan (GAG)-binding Chemokine

Determinants of Glycosaminoglycan (GAG) Structure

Proteoglycans (PGs) are glycosylated proteins of biological importance at cell surfaces, in the extracellular matrix, and in the circulation. PGs are produced and modified by glycosaminoglycan (GAG) chains in the secretory pathway of animal cells. The most common GAG attachment site is a serine residue followed by a glycine (-ser-gly-), from which a linker tetrasaccharide extends and may contin...

Engineering the glycosaminoglycan-binding affinity, kinetics and oligomerization behavior of RANTES: a tool for generating chemokine-based glycosaminoglycan antagonists.

Binding to glycosaminoglycans (GAGs) is a necessary prerequisite for the biological activity of the proinflammatory chemokine RANTES in vivo. We have applied protein engineering methods to modulate equilibrium-binding affinity as well as binding kinetics of RANTES towards its GAG ligand which also altered the chemokine's oligomerization behavior. Out of 10 mutants, A22K and H23K were chosen for...

Chemokine-Mediated Inflammation Chemoattractant Protein-3) Antagonizes of CC Chemokine Ligand 7 (Monocyte A Non-Glycosaminoglycan-Binding Variant

Interference with Oligomerization and Glycosaminoglycan Binding of the Chemokine CCL5 Improves Experimental Liver Injury

BACKGROUND The chemokine CCL5 is involved in the recruitment of immune cells and a subsequent activation of hepatic stellate cells (HSC) after liver injury. We here investigate whether inhibition of CCL5 oligomerization and glycosaminoglycan binding by a mutated CCL5 protein ((44)AANA(47)-CCL5) has the potential to ameliorate liver cell injury and fibrosis in vivo. METHODOLOGY Liver injury wa...

Structure and function of the glycosaminoglycan binding site of chemokine macrophage-inflammatory protein-1 beta.

The ability of chemokines to bind to glycosaminoglycans (GAGs) on cell surfaces and in the extracellular matrix is thought to play a crucial role in chemokine function. We investigated the structural basis for chemokine binding to GAGs by using in vitro mutagenesis to identify amino acids of chemokine macrophage-inflammatory protein-1 beta (MIP-1 beta) that contribute to its interaction with th...