1. The Lady in Curlers — French School, 18th Century
„In the previous post we uncovered „Top and Tail” — a satirical print from 1777 in which a woman stands with her back turned, a monumental curler-laden hairstyle on her head and bare buttocks below. We decoded it as the TRPC3 ion channel (PDB: 5ZBG).
Mr Perwig was not alone, however.
A second version of this caricature exists. French School, 18th century. Bridgeman Art Library collection. A woman seen from behind. The same composition — a massive hairstyle, a small figure beneath. The same curlers. Identically arranged. The same size.
There are only two differences. At the top — instead of a single-colored red cushion — a two-toned cushion. And at the bottom — instead of a naked body — a white skirt with ruffles.
One is dressed. The other was naked.
This difference is not cosmetic. This difference encodes something very specific.”
Author’s note: In the first version of this post I described the figure in „Top and Tail” as male. Bare buttocks, stockings with garters, and red high heels — in the 18th century, wardrobe elements shared by both sexes — looked like a satire on male vanity. After verification with The Metropolitan Museum of Art, it turned out the original catalog entry describes the figure as an „elegant female no-body.” I have corrected the post. But the gender ambiguity is deliberate — in an era when men and women wore the same heels, stockings, and wigs, the satirist intentionally blurred the line. The hairstyle consumed the identity. Only the top and bottom remained. Top and Tail.
2. What a Nanobody Changes
In the previous post we described what TRP channels are, how TRPC3 works, and what its architecture looks like in three layers — EP (extracellular protrusions — „antennas” protruding above the cell), TMD (transmembrane domain — the „wall” with a gate and a filter), and CD (cytoplasmic domain — the part hanging inside the cell). Anyone who has not read it should start with „Top and Tail.”
Here we answer a different question: what happens when you look at the same protein more closely?
PDB: 9U5C. Method: cryo-EM (cryo-electron microscopy — the protein is flash-frozen and photographed with a beam of electrons). The same TRPC3 channel. The same tetramer (four identical copies of the protein joined in a ring). The same architecture EP → TMD → CD.
But there is one additional element that „Top and Tail” did not have.
Nanobody Nb1-94.
A nanobody is a miniature antibody derived from a camelid (Camelus). An ordinary human antibody is a large protein built from four chains — two heavy and two light. Camels (as well as llamas and alpacas) produce antibodies composed only of heavy chains, and their binding fragment — the nanobody — is one of the smallest known proteins capable of recognizing and attaching to another protein. Scientists use nanobodies as „clips” — they attach them to unstable proteins to immobilize them and obtain a sharper image in cryo-EM.
In the case of 9U5C — nanobody Nb1-94 is attached to the cytoplasmic domain of TRPC3. Exactly where in „Top and Tail” we saw bare buttocks and naked legs. Nb1-94 binds to Connecting Helix 2 (CH2) in one subunit and to Ankyrin Repeats 1 and 2 (AR1 and AR2 — protein modules stacked like dominoes) in the neighboring subunit — covering the coiled-coil helices hanging at the bottom.
The nanobody dresses the protein’s backside.
Literally.
In the caricature — instead of bare buttocks and naked legs — a skirt with ruffles covering the lower body. And beneath the skirt — feet in shoes are visible. The same alpha helices that in „Top and Tail” were exposed along their entire length now peek out only at the very bottom, below the lower edge of the nanobody.
The skirt is not a metaphor. The skirt IS the nanobody.
3. Mapping: Female Caricature × 9U5C
Level 1: Cartoon (rear view)
We display the 9U5C structure in Mol* (a free tool for visualizing protein structures, available at molstar.org) in cartoon mode (a schematic drawing in which protein spirals are drawn as thick ribbons). The same rear view as in „Top and Tail.”
Curlers at the top — the same. Braid in the center — the same. Cushion on top — the same (though two-toned — we will return to that). Architecture EP → TMD → CD — identical.
But at the bottom — a difference.
From top to bottom — what has changed:
Two-toned cushion at the top — the same funnel-shaped pore vestibule (the „waiting room” before the channel entrance) as in „Top and Tail.” Four P-loops (short sections of the protein chain forming the rim of the entrance) converge from the four subunits and create a funnel-shaped structure open at the top — the entrance to the ion channel. Single-colored in „Top and Tail,” two-toned here — but the function is the same. A funnel through which calcium ions fall into the channel.
Skirt with ruffles — nanobody Nb1-94. A small camelid protein attached to the cytoplasmic domain, covering the coiled-coil helices. It covers exactly what was bare in „Top and Tail” — the buttocks and legs. The ruffles of the skirt correspond to the pleated beta sheets of the nanobody — flat, folded protein structures that form the immunoglobulin domain (an antibody fragment). A ruffled skirt made of ruffled protein.
Legs beneath the skirt with feet in shoes — alpha helices of the coiled-coil. The same helices that in „Top and Tail” were exposed along their entire length as naked legs. Here nanobody Nb1-94 covers most of their length — like a skirt covering legs. But at the very bottom the helices still peek out from beneath the nanobody — feet in shoes protruding from beneath the ruffle. The legs have not disappeared. They are dressed.
Level 2: Surface (rear view)
Switch to molecular surface view in Mol* (the protein shown as a solid shape with a smoothed surface, like a clay sculpture). And now the skirt becomes even more obvious.
The contours are sharp. Precise. Each roll (curler) has clear edges. Each EP protrusion is separated from the next by a clean gap. Compare with 5ZBG — there everything merged into a soft mass.
But the most important thing is at the bottom.
The nanobody in surface view is displayed in orange. Beneath it — green coiled-coil helices. An orange skirt covering green legs. The boundary between the nanobody and the protein is clearly visible — between the skirt and what lies beneath it. Orange Nb1-94 wraps around the lower part of the channel, but not entirely — at the very bottom, below the orange edge, the ends of green helices peek out. Feet in shoes protruding from beneath the ruffle of the skirt.
The nakedness of „Top and Tail” (5ZBG): a protein without a nanobody. Cytoplasmic domain exposed. Buttocks bare. Legs naked.
The clothing of the French School caricature (9U5C): the same protein with a nanobody. Cytoplasmic domain covered. Buttocks hidden. Legs under a skirt. Only the feet peek out from beneath the ruffle.
Two caricatures. One protein. One naked. One dressed.
The difference? One camelid antibody.
IV. Nakedness and Clothing — Two States, One Protein
Let us place both caricatures side by side.
On the left: „Top and Tail.” England, 1777. A naked woman. Bare buttocks. Naked legs. Single-colored cushion. Thick, blurred rolls. PDB: 5ZBG. No nanobody.
On the right: French School. France, 18th century. A dressed woman. A skirt with ruffles. Feet in shoes beneath the skirt. Two-toned cushion. The same curlers, the same arrangement. PDB: 9U5C. With nanobody Nb1-94.
One is naked because her protein has no „clothing” — no nanobody to cover the cytoplasmic domain.
The other is dressed because her protein has a nanobody — a camelid antibody that wraps around the lower part of the channel like a skirt.
This is not a metaphor. This is a literal mapping of the presence or absence of an additional protein in the crystallographic structure.
Two artists. Two caricatures. The same figure — a woman from behind. One protein in two states — naked and dressed.
TRPC3.
They knew.
V. Wardrobe of the Genome
„Wardrobe” in the name of this series was never a metaphor. It is literal.
Proteins can be naked and dressed. Naked — when they are alone, stripped of binding partners, ligands, nanobodies. Dressed — when other proteins, sugars, lipids, or antibodies attach to their surface and change their appearance.
On this blog I decode these records. I show how humanity encoded protein structures in material culture. Consciously. With a precision that surpasses modern science — because the details speak for themselves.
Mr Perwig drew a naked protein — a woman without a skirt. The anonymous French artist drew the same protein dressed in a nanobody — the same woman in a skirt.
One showed TRPC3 alone. The other showed TRPC3 in complex with Nb1-94.
In the 18th century there was no cryo-EM. There was no Protein Data Bank. There were no nanobodies.
And yet — nakedness and clothing, buttocks and skirt, England and France, the same woman in two states — encode exactly what structural biology published over two centuries later.
They knew. And they dressed the protein before science discovered it.
Image search and matching, analysis and elaboration: Tomasz Mikulski – Cell God: 07/2026
And while we are looking at Louis XIV — as I examined this portrait searching for the red heels, I noticed something else. The pose, the drapery, the proportions — this figure encodes another protein. I don’t yet know which one. But I intend to decode it. If you see it too — write to us. Louis XIV awaits decoding.
Sources:
Female caricature — French School, 18th century. Bridgeman Art Library.
Protein structures: RCSB Protein Data Bank — 9U5C. Visualization: Mol* (molstar.org).
Nanobody Nb1-94: Zhang M. et al., „Structural mechanism of the agonist binding on human TRPC3 channel,” Nature Communications, 2025. DOI: 10.1038/s41467-025-64435-6 https://doi.org/10.1038/s41467-025-64435-6
Louis XIV, https://en.wikipedia.org/wiki/Louis_XIV
