Structural basis for trypanosomal haem acquisition and susceptibility to the host innate immune system

Kristian Stødkilde, Morten Torvund-Jensen, Søren K. Moestrup and Christian B. F. Andersen ()
Additional contact information
Kristian Stødkilde: Aarhus University
Morten Torvund-Jensen: Aarhus University
Søren K. Moestrup: Aarhus University
Christian B. F. Andersen: Aarhus University

Nature Communications, 2014, vol. 5, issue 1, 1-8

Abstract: 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.

Date: 2014
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/ncomms6487 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6487

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms6487

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().