Evidence map›Paper›PMID 19706485›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2009

Selective reciprocity in antimicrobial activity versus cytotoxicity of hBD-2 and crotamine.

Nannette Y Yount, Deborah Kupferwasser, Alberto Spisni, Stephen M Dutz, Zachary H Ramjan, Shantanu Sharma, Alan J Waring, Michael R Yeaman

Open access · greenAbstract readComparative Study
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
4.4field-weighted citation impact, top 6% 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

50 citing papers in PubMed, 98 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. What Are the Neurotoxins in Hemotoxic Snake Venoms?International journal of molecular sciences · 2023
    Review
  6. Review
  7. SensitizingeLife · 2022
    Article
  8. Article
  9. Antimicrobial Peptides: An Update on Classifications and Databases.International journal of molecular sciences · 2021
    Review
  10. Review
  11. Membrane-Interacting Antifungal Peptides.Frontiers in cell and developmental biology · 2021
    Review
  12. Article
  13. Article
  14. Article
  15. Unifying structural signature of eukaryotic α-helical host defense peptides.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  16. Modulation of toll-like receptor signaling by antimicrobial peptides.Seminars in cell & developmental biology · 2019
    Review
  17. Article
  18. Article
  19. 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

8 authors at 5 institutions in 2 countries.

Nannette Y YountDivision of Infectious Diseases, LAC-Harbor University of California, Los Angeles Medical Center, Torrance, CA 90509, USA.
Deborah Kupferwasser
Alberto Spisni
Stephen M Dutz
Zachary H Ramjan
Shantanu Sharma
Alan J Waring
Michael R Yeaman
California State Polytechnic University · USThe Lundquist Institute · USLos Angeles Medical Center · USUniversity of California, Los Angeles · USUniversity of Parma · IT

Funding

Microbicidal Proteins from PlateletsR01AI039001 · NIAID · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · PI YEAMAN, MICHAEL R · 2006 to 2010
$1.7M
DETERMINANTS IN PLATELET MICROBICIDAL PROTEINSR01AI048031 · NIAID · LA BIOMED RES INST/ HARBOR UCLA MED CTR · PI YEAMAN, MICHAEL R · 2000 to 2004
$1.6M
NIAID NIH HHS 5R01AI39001NIAID NIH HHS 5R01AI48031NIAID NIH HHS R01 AI039001NIAID NIH HHS R01 AI048031
6 · The paper itself

Abstract

Recent discoveries suggest cysteine-stabilized toxins and antimicrobial peptides have structure-activity parallels derived by common ancestry. Here, human antimicrobial peptide hBD-2 and rattlesnake venom-toxin crotamine were compared in phylogeny, 3D structure, target cell specificity, and mechanisms of action. Results indicate a striking degree of structural and phylogenetic congruence. Importantly, these polypeptides also exhibited functional reciprocity: (i) they exerted highly similar antimicrobial pH optima and spectra; (ii) both altered membrane potential consistent with ion channel-perturbing activities; and (iii) both peptides induced phosphatidylserine accessibility in eukaryotic cells. However, the Na(v) channel-inhibitor tetrodotoxin antagonized hBD-2 mechanisms, but not those of crotamine. As crotamine targets eukaryotic ion channels, computational docking was used to compare hBD-2 versus crotamine interactions with prototypic bacterial, fungal, or mammalian Kv channels. Models support direct interactions of each peptide with Kv channels. However, while crotamine localized to occlude Kv channels in eukaryotic but not prokaryotic cells, hBD-2 interacted with prokaryotic and eukaryotic Kv channels but did not occlude either. Together, these results support the hypothesis that antimicrobial and cytotoxic polypeptides have ancestral structure-function homology, but evolved to preferentially target respective microbial versus mammalian ion channels via residue-specific interactions. These insights may accelerate development of anti-infective or therapeutic peptides that selectively target microbial or abnormal host cells.

Indexed as

CrotalusAmino Acid SequenceAnimalsAnti-Bacterial Agentsbeta-DefensinsBiophysical PhenomenaCells, CulturedCrotalid VenomsEscherichia coliHumansMicrobial ViabilityModels, MolecularMolecular Sequence DataPhylogenyProtein Structure, TertiarySequence AlignmentAnti-Bacterial Agentsbeta-DefensinsCrotalid VenomscrotamineDEFB4A protein, human

Identifiers

PMID19706485
PMCPMC2736466
OpenAlexW1995029980

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.