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

Kristian Stødkilde; Morten Torvund-Jensen; Søren K Moestrup; Christian B F Andersen

doi:10.1038/ncomms6487

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

Kristian Stødkilde, Morten Torvund-Jensen, Søren K Moestrup, Christian B F Andersen

Aarhus Universitet

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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 2-subunits of Hb (2Hb),with one receptor at each end of the dimeric Hp-Hb complex.The Hb 2-subunit haem group directly associates with the receptors, which allows for sensing of haem-containing Hp-Hb.The

Originalsprog	Engelsk
Artikelnummer	5487
Tidsskrift	Nature Communications
Vol/bind	5
Sider (fra-til)	5487
ISSN	2041-1723
DOI	https://doi.org/10.1038/ncomms6487
Status	Udgivet - 2014
Udgivet eksternt	Ja

Dokumenter og links

10.1038/ncomms6487

Citationsformater

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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 2-subunits of Hb (2Hb),with one receptor at each end of the dimeric Hp-Hb complex.The Hb 2-subunit haem group directly associates with the receptors, which allows for sensing of haem-containing Hp-Hb.The",

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AU - Stødkilde, Kristian

AU - Torvund-Jensen, Morten

AU - Moestrup, Søren K

AU - Andersen, Christian B F

PY - 2014

Y1 - 2014

N2 - 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 2-subunits of Hb (2Hb),with one receptor at each end of the dimeric Hp-Hb complex.The Hb 2-subunit haem group directly associates with the receptors, which allows for sensing of haem-containing Hp-Hb.The

AB - 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 2-subunits of Hb (2Hb),with one receptor at each end of the dimeric Hp-Hb complex.The Hb 2-subunit haem group directly associates with the receptors, which allows for sensing of haem-containing Hp-Hb.The

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

Abstract

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