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Phalloidin: The Death-Cap Mushroom Peptide That Became a Lab Stain for Actin

Phalloidin is a bicyclic peptide from the death-cap mushroom that locks actin filaments in place. Its toxicity is why it was studied; its grip on actin is why, since 1979, fluorescent phalloidin has been one of the standard ways to stain the cell skeleton under the microscope. It is not a medicine.

Natural toxinBicyclic peptideLab reagent — not a medicine

Caroline S · Published 2026-11-02

Length

A small cyclic peptide: molecular formula C35H48N8O11S, molecular weight 788.9 (PubChem CID 441542). ChEBI classes it as a homodetic cyclic peptide; its second ring is a tryptathionine bridge, the cross-link typical of the bicyclic Amanita peptides.

Sequence

Bicyclic: a peptide ring cross-linked by a tryptathionine bridge between a tryptophan and a cysteine (Biopolymers 2007, PMID 17626299). PubChem CID 441542 gives the full structure.

Origin

Made by the death-cap mushroom Amanita phalloides, which carries three groups of toxins: amatoxins, phallotoxins (phalloidin among them) and virotoxins (Food Chem Toxicol 2015, PMID 26375431).

Last reviewed

2026-11-02

What is it good for?

It is good for nothing as a treatment. It matters in two places: as one of the toxins of the death-cap mushroom, the species behind most fatal mushroom poisonings worldwide, and in the laboratory, where its tight binding to filamentous actin made fluorescent phalloidin a standard stain for the cell's skeleton since 1979. Suspected mushroom poisoning is a matter for a poison control centre or an emergency department, not for this page.

Illustration: A deep green death-cap mushroom on a white surface with soft shadows.
Illustration

What it is

Phalloidin is a small, doubly ringed peptide made by the death-cap mushroom. PubChem (CID 441542) gives its formula as C35H48N8O11S and its molecular weight as 788.9; ChEBI classes it as a homodetic cyclic peptide — one whose ring is closed entirely by peptide bonds. A second ring is formed by a tryptathionine bridge, a cross-link between a tryptophan and a cysteine that is characteristic of the bicyclic Amanita peptides (Biopolymers 2007, PMID 17626299).

It belongs to the phallotoxins, one of three toxin groups in Amanita phalloides. The other two are the amatoxins, of which alpha-amanitin is the best known, and the virotoxins (Food Chem Toxicol 2015, PMID 26375431; Toxicon 1998, PMID 9604278).

What it does

Actin is the protein that forms filaments in every cell's internal skeleton, assembling and disassembling constantly. A 1998 Toxicon review states that the phallotoxins "stimulate the polymerization of G-actin and stabilize the F-actin filaments" — single actin units are pushed into filaments, and the filaments are prevented from coming apart — and that the interaction runs through the toxin's small, 15-membered ring.

A 1978 review by Theodor Wieland and Heinz Faulstich (PMID 363352), covered the toxins' structures and their affinity for actin, and described antamanide, a cyclic peptide from the same mushrooms that counteracts phalloidin. In 2024 a Nature Communications study (PMID 39261469) used phalloidin-bound actin to image the structure of filament ends.

What is described How firm
Binds and stabilises actin filaments Biochemistry and structural work (1978–2024)
Works as a fluorescent actin stain Laboratory use since 1979
One of three toxin groups in death cap Toxicology reviews (1998, 2015)
Any use as a medicine None found

From toxin to stain

In 1979 Wieland's group made a fluorescent derivative of phalloidin with high affinity for filamentous actin and used it to visualise actin structures in cells (Wulf et al., PNAS, PMID 291981). Because the molecule is small, fixing cells with formaldehyde was enough to let it in. Fluorescent phalloidin has been a standard way to stain the cell skeleton ever since.

Poisoning

The death cap is involved in the majority of fatal mushroom poisonings worldwide (PMID 26375431). Phalloidin is one of its toxins, alongside the amatoxins and virotoxins; this entry does not apportion the poisoning among them, and nothing here is a guide to symptoms or treatment. Suspected mushroom poisoning is handled by a poison control centre — in the US, 1-800-222-1222 — or an emergency department.

Where it stands

  • Not a medicine, and no therapeutic use is recorded; a natural toxin and a research reagent.
  • Research volume: 4,628 PubMed records with phalloidin in the title or abstract, 79 of them also naming poisoning or intoxication; ClinicalTrials.gov lists 2 studies mentioning it (searched 2026-11-02).

Melittin is the library's entry on another natural toxin peptide, from bee venom, and peptide bonds explains how a ring can be closed by them.

What the research shows

Binds and stabilises actin filaments

Toxicon 1998 review (PMID 9604278): phallotoxins 'stimulate the polymerization of G-actin and stabilize the F-actin filaments'; 2024 cryo-EM structure of phalloidin-bound filament ends (Nat Commun, PMID 39261469)

Works as a microscope stain for actin

Wulf et al., PNAS 1979 (PMID 291981): a fluorescent derivative visualised actin structures in fixed cells

Contributes to death-cap poisoning

Death cap contains amatoxins, phallotoxins and virotoxins (PMID 26375431, 9604278); this entry does not apportion the poisoning among them

Any therapeutic use

None found; ClinicalTrials.gov lists 2 studies mentioning phalloidin (2026-11-02)

Bars show how much of the evidence is in humans, not how well anything works.

Where it stands

In nature

A toxin of the death-cap mushroom (Amanita phalloides).

In the laboratory

Used as fluorescent conjugates for staining F-actin in fixed cells — a research reagent, not for human use.

Published record

PubMed returns 4,628 records with phalloidin in the title or abstract, 79 of them also naming poisoning or intoxication; ClinicalTrials.gov lists 2 studies (2026-11-02).

Frequently asked questions

What is phalloidin?

A small bicyclic peptide made by the death-cap mushroom, Amanita phalloides. It binds actin filaments — part of every cell's internal skeleton — and locks them in place. It is a toxin and a laboratory reagent, not a medicine.

Is phalloidin what makes death caps deadly?

The death cap carries three groups of toxins — amatoxins, phallotoxins (including phalloidin) and virotoxins — according to clinical and toxicology reviews. This entry does not apportion the poisoning among them. Suspected mushroom poisoning is handled by poison control (in the US, 1-800-222-1222) or an emergency department.

Why is phalloidin used in labs?

Because it binds filamentous actin tightly and specifically. Since a 1979 paper from Theodor Wieland's group, phalloidin tagged with a fluorescent dye has been used to stain actin in fixed cells so the cell skeleton can be seen under a microscope.

How does phalloidin act on actin?

It promotes the assembly of actin into filaments and stabilises them so they do not come apart, according to a 1998 Toxicon review. A 2024 Nature Communications study used phalloidin-bound filaments to image how filament ends are stabilised.

Is phalloidin the same as alpha-amanitin?

No. Both are bicyclic peptides from the same mushroom, but alpha-amanitin is an amatoxin that blocks RNA polymerase, while phalloidin is a phallotoxin that acts on actin, as the 1978 Wieland and Faulstich review describes.