Evidence map›Paper›PMID 20145249›Full record

ArticleThe Journal of biological chemistry2010

Atypical alpha-conotoxin LtIA from Conus litteratus targets a novel microsite of the alpha3beta2 nicotinic receptor.

Sulan Luo, Kalyana Bharati Akondi, Dongting Zhangsun, Yong Wu, Xiaopeng Zhu, Yuanyan Hu, Sean Christensen, Cheryl Dowell, Norelle L Daly, David J Craik and 4 more

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
–field-weighted citation impact
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

30 citing papers in PubMed.

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  12. Review
  13. Discovery of peptide ligands through docking and virtual screening at nicotinic acetylcholine receptor homology models.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  14. Article
  15. Article
  16. Cloning, synthesis, and characterization of αO-conotoxin GeXIVA, a potent α9α10 nicotinic acetylcholine receptor antagonist.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  17. Article
  18. A novel α4/7-conotoxin LvIA from Conus lividus that selectively blocks α3β2 vs. α6/α3β2β3 nicotinic acetylcholine receptors.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014
    Article
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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

14 authors.

Sulan LuoKey Laboratory of Tropical Biological Resources, Ministry of Education, Ocean College, College of Materials and Chemical Engineering, Center for Experimental Biotechnology, Hainan University, Haikou Hainan 570228, China. luosulan2003@163.com
Kalyana Bharati Akondi
Dongting Zhangsun
Yong Wu
Xiaopeng Zhu
Yuanyan Hu
Sean Christensen
Cheryl Dowell
Norelle L Daly
David J Craik
Ching-I Anderson Wang
Richard J Lewis
Paul F Alewood
J Michael McIntosh

Funding

Venoms, Biological Resources, Molecular BiologyP01GM048677 · NIGMS · UNIVERSITY OF UTAH · PI OLIVERA, BALDOMERO M · 1993 to 2018
$32.2M
Novel Neuronal nAChR-Targeted PeptidesR01MH053631 · NIMH · UNIVERSITY OF UTAH · PI MCINTOSH, J MICHAEL · 2001 to 2011
$3.6M
NOVEL NEURONAL NACHR-TARGETED PEPTIDESR29MH053631 · NIMH · UNIVERSITY OF UTAH · PI MCINTOSH, J MICHAEL · 1996 to 2000
$107k
NIGMS NIH HHS GM48677NIGMS NIH HHS P01 GM048677NIMH NIH HHS MH53631NIMH NIH HHS R01 MH053631NIMH NIH HHS R29 MH053631
6 · The paper itself

Abstract

Different nicotinic acetylcholine receptor (nAChR) subtypes are implicated in learning, pain sensation, and disease states, including Parkinson disease and nicotine addiction. alpha-Conotoxins are among the most selective nAChR ligands. Mechanistic insights into the structure, function, and receptor interaction of alpha-conotoxins may serve as a platform for development of new therapies. Previously characterized alpha-conotoxins have a highly conserved Ser-Xaa-Pro motif that is crucial for potent nAChR interaction. This study characterized the novel alpha-conotoxin LtIA, which lacks this highly conserved motif but potently blocked alpha3beta2 nAChRs with a 9.8 nm IC(50) value. The off-rate of LtIA was rapid relative to Ser-Xaa-Pro-containing alpha-conotoxin MII. Nevertheless, pre-block of alpha3beta2 nAChRs with LtIA prevented the slowly reversible block associated with MII, suggesting overlap in their binding sites. nAChR beta subunit ligand-binding interface mutations were used to examine the >1000-fold selectivity difference of LtIA for alpha3beta2 versus alpha3beta4 nAChRs. Unlike MII, LtIA had a >900-fold increased IC(50) value on alpha3beta2(F119Q) versus wild type nAChRs, whereas T59K and V111I beta2 mutants had little effect. Molecular docking simulations suggested that LtIA had a surprisingly shallow binding site on the alpha3beta2 nAChR that includes beta2 Lys-79. The K79A mutant disrupted LtIA binding but was without effect on an LtIA analog where the Ser-Xaa-Pro motif is present, consistent with distinct binding modes.

Indexed as

Amino Acid SequenceAnimalsBinding SitesConotoxinsConus SnailFemaleIn Vitro TechniquesMiceModels, MolecularMolecular Sequence DataMutagenesis, Site-DirectedNicotinic AntagonistsNuclear Magnetic Resonance, BiomolecularOocytesOxidation-ReductionProtein FoldingConotoxinsNicotinic Antagonistsnicotinic receptor alpha3beta2Receptors, NicotinicRecombinant Proteins

Identifiers

PMID20145249
PMCPMC2852974

What OpenQuestion holds

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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.