Evidence map›Paper›PMID 14500876›Full record

ArticleProtein science : a publication of the Protein Society2003

The specificity of cross-reactivity: promiscuous antibody binding involves specific hydrogen bonds rather than nonspecific hydrophobic stickiness.

Leo C James, Dan S Tawfik

Open access · bronzeAbstract read
In one paragraph

Article in Protein science : a publication of the Protein Society, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
5.1field-weighted citation impact, top 5% 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

59 citing papers in PubMed, 140 citations in OpenAlex.

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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

2 authors at 2 institutions in 2 countries.

Leo C JamesMRC Laboratory of Molecular Biology, Cambridge CB2 2HQ, United Kingdom.
Dan S Tawfik
MRC Laboratory of Molecular Biology · GBWeizmann Institute of Science · IL

Funding

Wellcome Trust
6 · The paper itself

Abstract

Proteins are renowned for their specificity of function. There is, however, accumulating evidence that many proteins, from enzymes to antibodies, are functionally promiscuous. Promiscuity is of considerable physiological importance. In the immune system, cross-reactive or multispecific antibodies are implicated in autoimmune and allergy conditions. In most cases, however, the mechanism behind promiscuity and the relationship between specific and promiscuous activities are unknown. Are the two contradictory? Or can a protein exhibit several unrelated activities each of which is highly specific? To address these questions, we studied a multispecific IgE antibody (SPE7) elicited against a 2,4-dinitrophenyl hapten (DNP). SPE7 is able to distinguish between closely related derivatives such as NP (nitrophenol) and DNP, yet it can also bind a number of unrelated ligands. We find that, like DNP, the cross-reactants are themselves bound specifically-close derivatives of these cross-reactants show very low or no binding to SPE7. It has been suggested that cross-reactivity is simply due to "hydrophobic stickiness", nonspecific interactions between hydrophobic ligands and binding sites. However, partitioning experiments reveal that affinity for SPE7 is unrelated to ligand hydrophobicity. These data, combined with crystal structures of SPE7 in complex with four different ligands, demonstrate that each cross-reactant is bound specifically, forming different hydrogen bonds dependant upon its particular chemistry and the availability of complementary antibody residues. SPE7 is highly homologous to the germline antinitrophenol (NP) antibody B1-8. By comparing the sequences and binding patterns of SPE7 and B1-8, we address the relationship between affinity maturation, specificity, and cross-reactivity.

Indexed as

Hydrogen BondingHydrophobic and Hydrophilic InteractionsAmino Acid SequenceAnimalsAnthracenesAnthraquinonesAntibody AffinityAntibody SpecificityBase SequenceBinding, CompetitiveCloning, MolecularCross ReactionsCrystallography, X-RayDinitrophenolsEnzyme-Linked Immunosorbent AssayHaptensalizarinAnthracenesAnthraquinonesDinitrophenolsHaptensImmunoglobulin EImmunoglobulin Fab FragmentsImmunoglobulin Variable RegionNitrophenolsRecombinant ProteinsSchiff Bases

Identifiers

PMID14500876
PMCPMC2366915
OpenAlexW2097303612

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.