Scavenger receptor CD163 multimerises to allow uptake of diverse ligands
Scavenger receptors mediate cellular uptake of diverse ligands. CD163 is an archetypal scavenger receptor with a primary role in haemoglobin detoxification. Haemoglobin released from lysed erythrocytes causes oxidative damage. This is countered by formation of haemoglobin-haptoglobin complexes and CD163-mediated uptake into macrophages for degradation. Different haptoglobin isoforms form stoichiometrically diverse haptoglobin-haemoglobin complexes which must all be recognised by CD163. We show that CD163 forms multimeric complexes, with calcium-mediated interactions forming a trimeric base. Arms emerge from this base, moulding around the ligand to form a single promiscuous ligand-binding site. The arms can also bind to arms of adjacent protomers, blocking the ligand-binding surfaces in an autoinhibited state. This results in a scavenger receptor that can recognise diverse haemoglobin-containing complexes, allowing physiologically important detoxification.