Characterization of the binding of the globular domains of the complement component C1q to phosphatidylserine

C1q, the key component of the classical pathway of the Complement system, is known for its vast functional activity including clearance of apoptotic cells. The binding of C1q to apoptotic blebs occurs via an interaction with the phosphatidylserine externalized on the cell surface. In this study, we characterized the interaction between C1q and phosphatidylserine, with emphasis on the structure of the phosphatidylserine-binding site within the globular domains of C1q and the nature of binding of C1q with phosphatidylserine, using both in vitro and in silico methods. We established that all three globular fragments, forming one C1q globular domain, bound phosphatidylserine with the leading role of the phosphatidylserine-binding site pertaining to the A chain of the globular fragment of C1q. We also determined the closest-contact amino acids of C1q participating in the interaction with phosphatidylserine. An important role is suggested for the glycosylated Asn124 residue in the A chain of the globular fragment.