Evidence map›Paper›PMID 37622732›Full record

ArticlemAbs

Unique epitope-antibody interactions in the intrinsically disordered proteoglycan-like domain of human carbonic anhydrase IX defined by high-resolution NMR combined with yeast surface display.

Feng Ni, Cunle Wu, Ping Xu, Ping Wang, Yves Fortin, Melanie Arbour, Luke Masson, Denis L'Abbé, Andrea Acel, Mylene Gosselin and 1 more

Open access · goldAbstract read
In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 41% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. 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

11 authors at 1 institution in 1 country.

Feng NiHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.
Cunle WuHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.
Ping XuHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.
Ping WangHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.
Yves FortinHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.
Melanie ArbourHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.
Luke MassonHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.
Denis L'AbbéHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.
Andrea AcelHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.
Mylene GosselinHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.
Anne E G LenferinkHuman Health Therapeutics Research Centre, National Research Council Canada, Montreal, Quebec, Canada.
National Research Council Canada · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Carbonic anhydrase (CA)-IX is an extracellular enzyme that is essential in the adaptation of tumor cells to their increasingly more hypoxic and acidic microenvironment. Within the family of carbonic anhydrases, CA-IX is unique in that it is the only CA with an N-terminal intrinsically disordered region (IDR) containing a proteoglycan (PG)-like domain. This PG-like IDR has been described to be instrumental in CA-IX's enzyme activity, as well as tumor cell motility and invasion. We have characterized the antibody-epitope interactions of two novel and unique antibodies (11H9 and 12H8) that are specific for the human CA-IX's IDR. Binding interactions of these antibodies to the intact IDR were studied by surface plasmon resonance and high-resolution nuclear magnetic resonance (NMR) spectroscopy, while the specific epitopes were determined by both NMR and yeast surface display (YSD). Our data show that 12H8 binds to the N-terminus of CA-IX, while 11H9 has a high affinity for an epitope located in the central region of the IDR containing three GEEDLP repeats in a manner that is different from the previously described M75 antibody. Titration NMR spectroscopy using CA-IX's entire IDR in addition identified a secondary epitope of 11H9 at the beginning of the PG-like domain that remains exposed and available for further binding events after the engagement at its primary epitope at the center of the PG-like domain. Transverse relaxation optimized NMR spectroscopy of 11H9-F(Ab) in complex with the CA-IX IDR outlines structural rigidification of a linear epitope, while the rest of the IDR remains largely unstructured upon complex formation. This study illustrates how high-resolution NMR and YSD are used as complementary tools for a comprehensive characterization of antibody-epitope interactions involving intrinsically unstructured antigen domains with highly repetitive sequences.

Indexed as

Carbonic AnhydrasesSaccharomyces cerevisiaeAntigens, NeoplasmCarbonic Anhydrase IXEpitopesHumansMagnetic Resonance SpectroscopyProteoglycansAntigens, NeoplasmCarbonic Anhydrase IXCarbonic AnhydrasesEpitopesProteoglycansAntibodiesantibody–antigen interactionscarbonic anhydrase IXepitope mappingF(ab)intrinsically disordered proteinsNMR spectroscopyyeast surface display

Identifiers

PMID37622732
PMCPMC10461516
OpenAlexW4386151888

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.