STRUCTURE, FUNCTION AND CELLULAR EXPRESSION OF COMPLEMENT ANAPHYLATOXIN RECEPTORS

The past year has seen significant advances in determining the important structural-functional domains of the complement C5a anaphylatoxin receptor. The current model suggests a two-site binding motif in which part of the amino-terminal extracellular domain of the receptor is recognized first by the amino-terminal end and disulfide-linked core of the C5a ligand. This is followed by interaction of the carboxy-terminal end of C5a with a second, and as yet undefined, site on the receptor that results in activating appropriate signal transduction pathways via receptor coupled G proteins. Another recent advance has been the discovery that the C5a receptor is expressed on non-myeloid cells, suggesting that C5a confers previously unexpected functions on certain target tissue cells, including bronchial and alveolar epithelial cells, hepatocytes, astrocytes, and vascular endothelial cells.