Structural basis for ligand and innate immunity factor uptake by the trypanosome haptoglobin-haemoglobin receptor

DOI: 10.7554/eLife.05553
PMID: 25497229

Authors: Harriet Lane-serff (University of Oxford) , Paula Macgregor (University of Cambridge) , Ed Lowe (University of Oxford) , Mark Carrington (University of Cambridge) , Matthew K Higgins (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Elife , VOL 3

State: Published (Approved)
Published: December 2014

Abstract: The haptoglobin-haemoglobin receptor (HpHbR) of African trypanosomes allows acquisition of haem and provides an uptake route for trypanolytic factor-1, a mediator of innate immunity against trypanosome infection. In this study, we report the structure of Trypanosoma brucei HpHbR in complex with human haptoglobin-haemoglobin (HpHb), revealing an elongated ligand-binding site that extends along its membrane distal half. This contacts haptoglobin and the β-subunit of haemoglobin, showing how the receptor selectively binds HpHb over individual components. Lateral mobility of the glycosylphosphatidylinositol-anchored HpHbR, and a ∼50o kink in the receptor, allows two receptors to simultaneously bind one HpHb dimer. Indeed, trypanosomes take up dimeric HpHb at significantly lower concentrations than monomeric HpHb, due to increased ligand avidity that comes from bivalent binding. The structure therefore reveals the molecular basis for ligand and innate immunity factor uptake by trypanosomes and identifies adaptations that allow efficient ligand uptake in the context of the complex trypanosome cell surface. - See more at: http://elifesciences.org/content/3/e05553.full#sthash.VxBUnQfD.dpuf

Subject Areas: Biology and Bio-materials


Instruments: B21-High Throughput SAXS , I03-Macromolecular Crystallography