Abstract
Chemokines were described for their ability to recruit leukocytes and affect inflammatory. The functions have been controlled by their oligomerization states. CXCL4 (also named platelet factor 4, PF4) is the first chemokine identified with anti-angiogenesis function. Tetrameric CXCL4 has high affinity to Glycosaminoglycans (GAGs) while monomeric CXCL4 has be speculated to bind its protein receptor to trigger the downstream signal. For precisely executing the biological function, certain chemokine oligomers exist under different conditions. To control chemokine oligomerization relies on point mutations on residues at the oligomer interface. Interestingly, removal of disulfide linkages of CXCL4 modulates the oligomerization state from asymmetric tetramer to symmetric dimer. The factor is novel in controlling chemokine oligomers. To figure out the mechanism and dimer type, we checked molecular size, backbone solvent accessibility, and molecular dynamics based on R1, R2 and NOE measurements. We demonstrate that the N-terminal region is with great protection from solvent. We also reveal special dynamics in the N-terminal region. This result is different than other folded chemokines. We speculate that DTT-reduced CXCL4 more likely adopts CC-type dimer fold. To directly answer the question, structural determination will be required in the future.