Structural elucidation of the haptoglobin–hemoglobin clearance mechanism by macrophage scavenger receptor CD163
Fig 5
Schematics of proposed mechanism for haptoglobin–hemoglobin clearance mediated by CD163.
During intravascular hemolysis, haptoglobins seize released hemoglobin forming HpHb complexes. Only dimeric Hp(1–1)Hb, trimeric Hp(2–1)Hb and tetrameric Hp(2–2)Hb structures are shown here for simplicity. On the cell surface, CD163 predominantly forms autoinhibitory trimers prior to ligand binding. During HpHb uptake, CD163 transitions from inactive to active state trimers through a uniform recognition mechanism across different multimeric forms of HpHb. During the ongoing constitutive (left) or ligand-dependent (right) receptor internalization and recycling, the CD163-HpHb complexes disassemble upon reaching the endosome (due to low pH and low Ca+2 concentration), resulting in subsequent ligand release. The dissociated HpHb complexes are transferred to lysosome for degradation, while the dissociated receptors are recycled back to the cell surface and reassemble into CD163 trimers.