Strength in numbers: how multimerization drives HpHb uptake by CD163 scavenging receptor.

De Bei, Omar; Campanini, Barbara · Nat Commun · 2025

basic_science · Level V

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Abstract

CD163 is a macrophage scavenger receptor central to the clearance of haptoglobin-hemoglobin (HpHb) complexes and the resolution of inflammation. In a remarkable example of near-simultaneous scientific progress, three complementary studies published in Nature Communications<sup>–</sup> have resolved the near-atomic resolution structure of the full extracellular domain of human CD163 complexed with HpHb, primarily utilizing cryo-electron microscopy (cryo-EM). The most significant and unified conclusion emerging from this trio of papers is that CD163’s scavenging activity is fundamentally dependent on its ability to form functional multimers.