Epic Quest Bio The case files
Case No. 116 · the exotic forty · have you seen this molecule?

MscS

a.k.a. “The Doorman” · the bacterial emergency release valve

In The Demon Job he's the Doorman: a channel that opens when the membrane stretches and doesn't look at who goes through, which is why the Demon's door job didn't work out.

A frame from The Demon Job
The film · 31 minutes

MscS plays The Doorman in The Demon Job

A detective made of water, a client who was the first molecule there ever was, and a demon who says he can sort for nothing.

Watch from 10:50, where The Doorman first appears → or from the start

Booking photographs

MscS, front view, against a height chart in nanometers
FRONT
MscS, side view
SIDE · PDB 2OAU

The suspect, from its real atomic coordinates. Drag to turn it. Height chart in nanometers, ruled every 0.5 nm. An E. coli is about 160 times longer.

Rap sheet

  1. Opening unaided: membrane tension alone pulls it open, just short of the cell bursting.
  2. Not looking: lets ions and small molecules out by the crowd, not by the face.
  3. A misleading mugshot: its first structure looked open; it was a vapor lock, two rings of leucines too greasy for water to wet.
  4. Being heard before it was seen: caught snapping open on a patch-clamp pipette in 1987.
  5. Family connections: a cousin, Flycatcher1, sits in the Venus flytrap's trigger hairs.
Answers to
Mechanosensitive channel of small conductance. Alias YggB.
Height
12.4 nm, membrane end up, cage down.
Weight
360 zeptograms, in seven identical parts.
Build
21 helices in the membrane over a hollow cage with seven 1 nm side windows.
Habits
Opens, unaided, when the stretched cell is just short of bursting.
Alibi
Its first mugshot looked wide open. It wasn’t: two rings of leucines too greasy for water to wet.
Associates
A cousin, Flycatcher1, sits in the Venus flytrap’s trigger hairs.
Last seen
In the inner membrane of E. coli, including the ones in your gut.
M.O.
When a bacterium drops into fresh water, water rushes in and stretches the inner membrane. Lipids tucked into grooves between its helices pull away, and the seven-part channel opens, letting solutes out through its side windows until the pressure falls.
Associates
MscL, its bigger cousin and the last-ditch valve; Flycatcher1, in the Venus flytrap; gatekeeper lipids; E. coli, a few hundred channels to a cell
Priors
Heard in 1987 on giant E. coli spheroplasts; crystal structure in 2002 (called open, later shown non-conducting); the vapor lock described in 2004 and 2008; the gatekeeper lipids in 2021.
410

of them in one E. coli on a sugar diet, give or take.
Diets vary. You’ve never seen one.

CASE FILE: Bass, R. B. et al. (2002) Crystal structure of Escherichia coli MscS, a voltage-modulated and mechanosensitive channel. Science 298, 1582–1587.

“A door that opens for pressure, not for faces. Nothing to know, nothing to sort.” — Keltar, on the case

Case notes: the note, and the valve

Maxwell's catechism 'Concerning Demons' was written to Tait about 1875. It must postdate 1874, because it answers 'Who gave them this name?' with 'Thomson'. Its fourth answer: 'less intelligent demons can produce a difference in pressure as well as temperature by merely allowing all particles going in one direction to pass while stopping all those going the other way. This reduces the demon to a valve. As such value him. Call him no more a demon but a valve like that of the hydraulic ram, suppose.' In 1912 Smoluchowski explained why no valve can do the job at one temperature: 'the valve has its own tendency to fluctuate.' One of his candidate devices was a ring of cilia.

MscS opens on membrane tension alone, with a slight preference for anions; it looks at nothing. MscS and MscL are the cell's 'emergency release valves'. A cell adapted to salty water and suddenly diluted must shed about five hundred million solute molecules in a few milliseconds, solutes it spent energy to accumulate, and the membrane potential collapses as it does.

Sources
  • Maxwell J. C., 'Concerning Demons', c. 1875, Cambridge Digital Library PH-CAVENDISH-P-00091; printed in Knott C. G. 1911, Life and Scientific Work of Peter Guthrie Tait, pp. 214-215
  • Smoluchowski M. 1912, Phys. Z. 13:1069-1080
  • Bass R. B. et al. 2002, Science 298:1582-1587, doi:10.1126/science.1077945
  • Sukharev S. 2002, Biophys. J. (tension gating; anion preference)
  • Booth I. R. 2014, Curr. Opin. Microbiol., doi:10.1016/j.mib.2014.01.005

The interrogation room

Keltar, the one-eyed felt detective
Keltar, night shift. Everything he knows about this suspect is in the file.

Keltar is an AI character. He sticks to the file; the conversation is saved and Kent, the CEO, can read it.

The poster on the street

The wanted poster for MscS

This is the photocopied wanted poster for MscS, No. 116 of the exotic forty. They were made for noticeboards around Boston, Cambridge and the rest of the east coast.

Found one? Scan its QR code with your phone. If you're a signed-in player, the sighting goes on your record with +1 XP.

Not a player yet? Join the Epic Quest: the real role-playing game of Molecular Reality, a nanopore lab, with the CEO as gamemaster.