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bioRxiv · 10.1101/2024.12.18.629151

Scavenger receptor CD163 multimerises to allow uptake of diverse ligands

Zhou, R. X.·Higgins, M. K.
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Abstract

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.

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Zhou, R. X., Higgins, M. K.. 2024-12-20. Scavenger receptor CD163 multimerises to allow uptake of diverse ligands. https://doi.org/10.1101/2024.12.18.629151

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