Structural basis for oligomerization and glycosaminoglycan binding of CCL5 and CCL3
Copyright policy )Structural basis for oligomerization and glycosaminoglycan binding of CCL5 and CCL3
SignificanceOligomerization and glycosaminoglycan (GAG) binding are key regulatory steps for many extracellular ligands. Our analyses provide a structural basis of CC chemokine ligand 5 (CCL5) and CCL3 oligomerization and explain how oligomerization affects the interaction of these chemokines with GAG and their functions. Our GAG-bound chemokine structures reveal how CCL5 and CCL3 oligomerization creates distinctive GAG-binding grooves to enhance GAG binding via avidity for regulating chemokine functions. Furthermore, our CCL5 structure may explain how CXCL4, a CXC chemokine, heterooligomerizes with CCL5 to modulate chemokine-mediated activities. Together, these data provide new structural insights into how oligomerization and GAG binding are coupled to regulate functions of CC chemokines and offer novel pharmacophores for the design of therapeutics for treating chemokine-mediated human diseases.
- University College London United Kingdom
- THE UNIVERSITY OF CHICAGO
- Department of Chemistry Austria
- The University of Chicago United States
- Academia Sinica Taiwan
Binding Sites, Protein Conformation, protein oligomerization, CC chemokine, Structure-Activity Relationship, glycosaminoglycan, Humans, Chemokine CCL5, Dimerization, signal transduction, X-ray crystallography, Chemokine CCL3, Glycosaminoglycans, Protein Binding
Binding Sites, Protein Conformation, protein oligomerization, CC chemokine, Structure-Activity Relationship, glycosaminoglycan, Humans, Chemokine CCL5, Dimerization, signal transduction, X-ray crystallography, Chemokine CCL3, Glycosaminoglycans, Protein Binding
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