Evidence map›Paper›PMID 19837661›Full record

ArticleThe Journal of biological chemistry2009

Heparan sulfate phage display antibodies identify distinct epitopes with complex binding characteristics: insights into protein binding specificities.

Sophie M Thompson, David G Fernig, Edwin C Jesudason, Paul D Losty, Els M A van de Westerlo, Toin H van Kuppevelt, Jeremy E Turnbull

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

29 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Expression of the Extracellular SulfataseFrontiers in oncology · 2020
    Article
  10. Proteomics, Glycomics, and Glycoproteomics of Matrisome Molecules.Molecular & cellular proteomics : MCP · 2019
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Heparin sensing: blue-chip binding.Nature chemistry · 2013
    Article
  19. An introduction to proteoglycans and their localization.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2012
    Review
  20. Article
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

7 authors at 4 institutions in 2 countries.

Sophie M ThompsonSchool of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, United Kingdom.
David G Fernig
Edwin C Jesudason
Paul D Losty
Els M A van de Westerlo
Toin H van Kuppevelt
Jeremy E Turnbull
University of Liverpool · GBAlder Hey Children's Hospital · GBRadboud University Medical Center · NLRadboud University Nijmegen · NL

Funding

Biotechnology and Biological Sciences Research CouncilMedical Research Council G0802057
6 · The paper itself

Abstract

Heparan sulfate (HS) binds and modulates the transport and activity of a large repertoire of regulatory proteins. The HS phage display antibodies are powerful tools for the analysis of native HS structure in situ; however, their epitopes are not well defined. Analysis of the binding specificities of a set of HS antibodies by competitive binding assays with well defined chemically modified heparins demonstrates that O-sulfates are essential for binding; however, increasing sulfation does not necessarily correlate with increased antibody reactivity. IC50 values for competition with double modified heparins were not predictable from IC50 values with corresponding singly modified heparins. Binding assays and immunohistochemistry revealed that individual antibodies recognize distinct epitopes and that these are not single linear sequences but families of structurally similar motifs in which subtle variations in sulfation and conformation modify the affinity of interaction. Modeling of the antibodies demonstrates that they possess highly basic CDR3 and surrounding surfaces, presenting a number of possible orientations for HS binding. Unexpectedly, there are significant differences between the existence of epitopes in tissue sections and observed in vitro in dot blotted tissue extracts, demonstrating that in vitro specificity does not necessarily correlate with specificity in situ/vivo. The epitopes are therefore more complex than previously considered. Overall, these data have significance for structure-activity relationships of HS, because the model of one antibody recognizing multiple HS structures and the influence of other in situ HS-binding proteins on epitope availability are likely to reflect the selectivity of many HS-protein interactions in vivo.

Indexed as

Antibody AffinityAntibody SpecificityAmino Acid MotifsAnimalsAntibodies, MonoclonalBinding Sites, AntibodyEpitopesHeparan SulfateMiceRatsRats, Sprague-DawleyAntibodies, MonoclonalEpitopesHeparan Sulfate

Identifiers

PMID19837661
PMCPMC2790993
OpenAlexW2024454200

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.