4WJG

Structure of T. brucei haptoglobin-hemoglobin receptor binding to human haptoglobin-hemoglobin

Summary for 4WJG

• Entry DOI: 10.2210/pdb4wjg/pdb
• Descriptor: Hemoglobin subunit alpha, Hemoglobin subunit beta, Haptoglobin, ... (9 entities in total)
• Functional Keywords: endocytosis, trypanosome, receptor
• Biological source: Staphylococcus aureus subsp. aureus N315; More
• Total number of polymer chains: 30
• Total formula weight: 737316.68

Authors

Stoedkilde, K.,Torvund-Jensen, M.,Moestrup, S.K.,Andersen, C.B.F. (deposition date: 2014-09-30, release date: 2014-11-26, Last modification date: 2024-10-16)

Primary citation

Stdkilde, K.,Torvund-Jensen, M.,Moestrup, S.K.,Andersen, C.B.
Structural basis for trypanosomal haem acquisition and susceptibility to the host innate immune system.
Nat Commun, 5:5487-5487, 2014

PubMed Abstract: Sleeping sickness is caused by trypanosome parasites, which infect humans and livestock in Sub-Saharan Africa. Haem is an important growth factor for the parasites and is acquired from the host by receptor-mediated uptake of haptoglobin (Hp)-haemoglobin (Hb) complexes. The parasite Hp-Hb receptor (HpHbR) is also a target for a specialized innate immune defence executed by trypanosome-killing lipoprotein particles containing an Hp-related protein in complex with Hb. Here we report the structure of the multimeric complex between human Hp-Hb and Trypanosoma brucei brucei HpHbR. Two receptors forming kinked three-helical rods with small head regions bind to Hp and the β-subunits of Hb (βHb), with one receptor at each end of the dimeric Hp-Hb complex. The Hb β-subunit haem group directly associates with the receptors, which allows for sensing of haem-containing Hp-Hb. The HpHbR-binding region of Hp is conserved in Hp-related protein, indicating an identical recognition of Hp-Hb and trypanolytic particles by HpHbR in human plasma.

PubMed: 25410714
DOI: 10.1038/ncomms6487

Experimental method

X-RAY DIFFRACTION (3.1 Å)