4WJG: Structure of T. brucei haptoglobin-hemoglobin receptor binding to human haptoglobin-hemoglobin

Citation:
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 beta-subunits of Hb (betaHb), with one receptor at each end of the dimeric Hp-Hb complex. The Hb beta-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.
PDB ID: 4WJGDownload
MMDB ID: 125132
PDB Deposition Date: 2014/9/30
Updated in MMDB: 2014/12
Experimental Method:
x-ray diffraction
Resolution: 3.1  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 4WJG: decameric; determined by author
Molecular Components in 4WJG
Label Count Molecule
Proteins (10 molecules)
2
Hemoglobin Subunit Alpha(Gene symbol: HBA1)
Molecule annotation
2
Hemoglobin Subunit Beta(Gene symbol: HBB)
Molecule annotation
2
Haptoglobin(Gene symbol: HP)
Molecule annotation
2
Iron-regulated Surface Determinant Protein H
Molecule annotation
2
Haptoglobin-hemoglobin Receptor
Molecule annotation
Chemicals (22 molecules)
1
4
2
4
3
14
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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