PDBsum entry 4x0l

Oxygen transport

PDB id: 4x0l

Contents

Protein chains

141 a.a.

144 a.a.

259 a.a.

Ligands

NAG-FUC

HEM-OXY ×2

GOL ×2

SO4

CAC

Waters ×217

PDB id:

4x0l

Name:

Oxygen transport

Title:

Human haptoglobin-haemoglobin complex

Structure:

Hemoglobin subunit alpha. Chain: a. Synonym: alpha-globin,hemoglobin alpha chain. Engineered: yes. Hemoglobin subunit beta. Chain: b. Synonym: beta-globin,hemoglobin beta chain. Engineered: yes. Haptoglobin.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hba1, hba2. Expressed in: homo sapiens. Expression_system_taxid: 9606. Gene: hbb. Gene: hp. Expressed in: spodoptera frugiperda.

Resolution:

2.05Å R-factor: 0.182 R-free: 0.224

Authors:

H.Lane-Serff,P.Macgregor,E.D.Lowe,M.Carrington,M.K.Higgins

Key ref:

H.Lane-Serff et al. (2014). Structural basis for ligand and innate immunity factor uptake by the trypanosome haptoglobin-haemoglobin receptor. Elife, 3, e05553. PubMed id: 25497229 DOI: 10.7554/eLife.05553

Date:

21-Nov-14 Release date: 24-Dec-14

Protein chain

P69905  (HBA_HUMAN) -  Hemoglobin subunit alpha from Homo sapiens

Seq: 142 a.a.

Struc: 141 a.a.

Protein chain

P68871  (HBB_HUMAN) -  Hemoglobin subunit beta from Homo sapiens

Seq: 147 a.a.

Struc: 144 a.a.

Protein chain

P00738  (HPT_HUMAN) -  Haptoglobin from Homo sapiens

Seq: 406 a.a.

Struc: 259 a.a.

DOI no: 10.7554/eLife.05553

Elife 3:e05553 (2014)

PubMed id: 25497229

Structural basis for ligand and innate immunity factor uptake by the trypanosome haptoglobin-haemoglobin receptor.

H.Lane-Serff, P.MacGregor, E.D.Lowe, M.Carrington, M.K.Higgins.

ABSTRACT

The haptoglobin-haemoglobin receptor (HpHbR) of African trypanosomes allows acquisition of haem and provides an uptake route for trypanolytic factor-1, a mediator of innate immunity against trypanosome infection. In this study, we report the structure of Trypanosoma brucei HpHbR in complex with human haptoglobin-haemoglobin (HpHb), revealing an elongated ligand-binding site that extends along its membrane distal half. This contacts haptoglobin and the β-subunit of haemoglobin, showing how the receptor selectively binds HpHb over individual components. Lateral mobility of the glycosylphosphatidylinositol-anchored HpHbR, and a ∼50° kink in the receptor, allows two receptors to simultaneously bind one HpHb dimer. Indeed, trypanosomes take up dimeric HpHb at significantly lower concentrations than monomeric HpHb, due to increased ligand avidity that comes from bivalent binding. The structure therefore reveals the molecular basis for ligand and innate immunity factor uptake by trypanosomes and identifies adaptations that allow efficient ligand uptake in the context of the complex trypanosome cell surface.