Evidence map›Paper›PMID 23319650›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2013

Structure of the trypanosome haptoglobin-hemoglobin receptor and implications for nutrient uptake and innate immunity.

Matthew K Higgins, Olga Tkachenko, Alan Brown, Jenny Reed, Jayne Raper, Mark Carrington

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
6.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 77 citations in OpenAlex.

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  9. Haptoglobin polymorphism affects its N-glycosylation pattern in serum.Journal of mass spectrometry and advances in the clinical lab · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Matthew K HigginsDepartment of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom.
Olga Tkachenko
Alan Brown
Jenny Reed
Jayne Raper
Mark Carrington
University of Cambridge · GBHunter College · USUniversity of Oxford · GB

Funding

Wellcome TrustWellcome Trust 085256/Z/08/ZWellcome Trust 087692/Z/08/Z
6 · The paper itself

Abstract

African trypanosomes are protected by a densely packed surface monolayer of variant surface glycoprotein (VSG). A haptoglobin-hemoglobin receptor (HpHbR) within this VSG coat mediates heme acquisition. HpHbR is also exploited by the human host to mediate endocytosis of trypanolytic factor (TLF)1 from serum, contributing to innate immunity. Here, the crystal structure of HpHbR from Trypanosoma congolense has been solved, revealing an elongated three α-helical bundle with a small membrane distal head. To understand the receptor in the context of the VSG layer, the dimensions of Trypanosoma brucei HpHbR and VSG have been determined by small-angle X-ray scattering, revealing the receptor to be more elongated than VSG. It is, therefore, likely that the receptor protrudes above the VSG layer and unlikely that the VSG coat can prevent immunoglobulin binding to the receptor. The HpHb-binding site has been mapped by single-residue mutagenesis and surface plasmon resonance. This site is located where it is readily accessible above the VSG layer. A single HbHpR polymorphism unique to human infective T. brucei gambiense has been shown to be sufficient to reduce binding of both HpHb and TLF1, modulating ligand affinity in a delicate balancing act that allows nutrient acquisition but avoids TLF1 uptake.

Indexed as

Amino Acid SequenceAnimalsBinding SitesEndocytosisHost-Parasite InteractionsHumansImmunity, InnateModels, MolecularMolecular Sequence DataMutationProtein BindingProtein Structure, SecondaryProtein Structure, TertiaryReceptors, Cell SurfaceScattering, Small AngleSequence Homology, Amino Acidhemoglobin-haptoglobin receptorReceptors, Cell SurfaceVariant Surface Glycoproteins, Trypanosoma

Identifiers

PMID23319650
PMCPMC3562850
OpenAlexW1974141262

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.