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Cited by 32Venomous Animal Envenomation and StudiesProtein Interaction Studies and Fluorescence AnalysisAmphibian and Reptile Biology

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Binding and sequestration of poison frog alkaloids by a plasma globulin

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Alvarez-Buylla, Aurora, Fischer, Marie-Therese, Moya Garzon, Maria Dolores, Rangel, Alexandra E, Tapia, Elicio E, Tanzo, Julia T, Soh, H Tom, Coloma, Luis A, Long, Jonathan Z, O'Connell, Lauren A·2023·eLife
DOI 10.7554/elife.85096PMC PMC10783871

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Abstract

Alkaloids are important bioactive molecules throughout the natural world, and in many animals they serve as a source of chemical defense against predation. Dendrobatid poison frogs bioaccumulate alkaloids from their diet to make themselves toxic or unpalatable to predators. Despite the proposed roles of plasma proteins as mediators of alkaloid trafficking and bioavailability, the responsible proteins have not been identified. We use chemical approaches to show that a ~50 kDa plasma protein is the principal alkaloid-binding molecule in blood of poison frogs. Proteomic and biochemical studies establish this plasma protein to be a liver-derived alkaloid-binding globulin (ABG) that is a member of the serine-protease inhibitor (serpin) family. In addition to alkaloid-binding activity, ABG sequesters and regulates the bioavailability of ‘free’ plasma alkaloids in vitro. Unexpectedly, ABG is not related to saxiphilin, albumin, or other known vitamin carriers, but instead exhibits sequence and structural homology to mammalian hormone carriers and amphibian biliverdin-binding proteins. ABG represents a new small molecule binding functionality in serpin proteins, a novel mechanism of plasma alkaloid transport in poison frogs, and more broadly points toward serpins acting as tunable scaffolds for small molecule binding and transport across different organisms.

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Metadata

Authors
Alvarez-Buylla, A., Fischer, M.-T., Moya Garzon, M. D., Rangel, A. E., Tapia, E. E., Tanzo, J. T., Soh, H. T., Coloma, L. A., Long, J. Z., & O'Connell, L. A.
Affiliations
  • Department of Biology, Stanford University
  • Stanford University (US)
  • Sarafan ChEM-H, Stanford University
  • Leibniz Institute for the Analysis of Biodiversity Change (DE)
  • Chan Zuckerberg Biohub
  • Centro Jambatu de Investigación y Conservación de Anfibios (EC)
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2023-12-19
Volume
12
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.85096
PMC
PMC10783871
OpenAlex
W4390776898
Cited by
32
References
5
Citations by year
2026: 9 · 2025: 5 · 2024: 13 · 2023: 4
FWCI
5.15
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Science Foundation (IOS-1822025)
  • New York Stem Cell Foundation
  • National Science Foundation Graduate Research Fellowship Program (DGE-1656518)
  • Howard Hughes Medical Institute (GT13330)
  • Fundacion Alfonso Martin Escudero
  • Wu Tsai Human Performance Alliance
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Venomous Animal Envenomation and Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Interaction Studies and Fluorescence Analysis
  • Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Amphibian and Reptile Biology
Keywords
serpins, serine protease inhibitors, plasma protein binding, alkaloid sequestration, chemical defense, albumin, Dendrobatidae
MeSH terms
Poison Frogs, Alkaloids, Animals, Anura, Blood Proteins, Globulins, Mammals, Serpins, Proteomics

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