PDBsum entry 4wjg

Endocytosis

PDB id: 4wjg

Contents

Protein chains

(+ 0 more) 141 a.a.

(+ 0 more) 146 a.a.

(+ 0 more) 310 a.a.

(+ 0 more) 144 a.a.

(+ 0 more) 261 a.a.

Ligands

NAG-NAG ×10

HEM-OXY ×12

NAG ×23

PDB id:

4wjg

Name:

Endocytosis

Title:

Structure of t. Brucei haptoglobin-hemoglobin receptor binding to human haptoglobin-hemoglobin

Structure:

Hemoglobin subunit alpha. Chain: a, f, k, p, u, z. Synonym: alpha-globin,hemoglobin alpha chain. Hemoglobin subunit beta. Chain: b, g, l, q, v, 1. Synonym: beta-globin,hemoglobin beta chain. Haptoglobin. Chain: c, h, m, r, w, 2. Synonym: zonulin.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Staphylococcus aureus subsp. Aureus n315. Organism_taxid: 158879. Gene: isdh, hara, sasi, sa1552. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Trypanosoma brucei brucei.

Resolution:

3.10Å R-factor: 0.255 R-free: 0.271

Authors:

K.Stoedkilde,M.Torvund-Jensen,S.K.Moestrup,C.B.F.Andersen

Key ref:

K.Stødkilde et al. (2014). Structural basis for trypanosomal haem acquisition and susceptibility to the host innate immune system. Nat Commun, 5, 5487. PubMed id: 25410714 DOI: 10.1038/ncomms6487

Date:

30-Sep-14 Release date: 26-Nov-14

Protein chains

P69905  (HBA_HUMAN) -  Hemoglobin subunit alpha from Homo sapiens

Seq: 142 a.a.

Struc: 141 a.a.

Protein chains

P68871  (HBB_HUMAN) -  Hemoglobin subunit beta from Homo sapiens

Seq: 147 a.a.

Struc: 146 a.a.

Protein chains

P00738  (HPT_HUMAN) -  Haptoglobin from Homo sapiens

Seq: 406 a.a.

Struc: 310 a.a.

Protein chains

Q99TD3  (ISDH_STAAN) -  Iron-regulated surface determinant protein H from Staphylococcus aureus (strain N315)

Seq: 891 a.a.

Struc: 144 a.a.

Protein chains

I7BA80  (I7BA80_TRYBB) -  Haptoglobin-hemoglobin receptor from Trypanosoma brucei brucei

Seq: 403 a.a.

Struc: 261 a.a.

DOI no: 10.1038/ncomms6487

Nat Commun 5:5487 (2014)

PubMed id: 25410714

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

K.Stødkilde, M.Torvund-Jensen, S.K.Moestrup, C.B.Andersen.

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.