Case No. 138 · the exotic forty · have you seen this molecule?

KaiC clock protein

a.k.a. “The Old Man” · a day, kept by three proteins

In The Demon Job he's the Old Man: a clock protein keeping a day in a test tube on about fifteen ATP a day per part, until somebody starts taking his ATP.

The film · 31 minutes

KaiC clock protein plays The Old Man 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 0:00, where The Old Man first appears → or from the start

Booking photographs

KaiC clock protein, front view, against a height chart in nanometers — FRONT

KaiC clock protein, side view — SIDE · PDB 1TF7

The suspect, from its real atomic coordinates. Drag to turn it. Height chart in nanometers, a line every 2 nm. The cyanobacterium it keeps time for is about two hundred times longer.

Rap sheet

Keeping time without a cell: KaiA, KaiB, KaiC and ATP oscillate in a test tube (2005).
Living cheap: about 15 ATP per subunit per day, where its relatives burn thousands to millions.
Temperature compensation: about 24 hours, warm or cool.
Holding a water molecule in an awkward spot, which is why it is so slow.
Keeping a strict routine: two phosphates on, two off, always in the same order.

Answers to: KaiC. “Kai” is Japanese for “cycle.”
Height: 10.7 nm, two rings tall.
Weight: 590 zeptograms, ATPs included.
Build: A double doughnut: six parts, two rings, one pore.
Habits: Puts two phosphates on and takes them off, once a day, always in the same order.
Secret: Holds a water molecule in an awkward spot. Hence the slowness.
Associates: KaiA winds it up. KaiB changes its whole fold, then takes KaiA away.
Alibi: About 24 hours, warm or cool.
Last seen: In freshwater cyanobacteria, and ticking in test tubes.
M.O.: KaiA pushes KaiC to phosphorylate itself, first at threonine 432, then at serine 431. Once loaded, KaiC binds KaiB, which switches to a different fold and takes KaiA away; KaiC then strips its phosphates in a fixed order. One lap takes about a day.
Associates: KaiA, which winds it up; KaiB, which changes its whole fold, then takes KaiA away; Synechococcus elongatus, the freshwater cyanobacterium it keeps time for; ATP
Priors: Gene cluster named kaiABC ('kai' is Japanese for 'cycle'); crystal structure in 2004; the test-tube clock in 2005; its ATP bill and the ordered phosphorylation cycle in 2007; the water molecule behind the slowness in 2015.

ATP a day is all each of its six parts burns. Its relatives burn thousands.
You’ve never seen one.

CASE FILE: Nakajima, M. et al. (2005) Reconstitution of circadian oscillation of cyanobacterial KaiC phosphorylation in vitro. Science 308, 414–415.

“Ninety ATP a day for the whole ring. Cheap. Not free.” — Keltar, on the case

Case notes: what a good clock costs

KaiC burns about 15 ATP per subunit per day (14.5 on its own, 15.8 with KaiA and KaiB, at 30 °C). The tube normally starts with 1 mM ATP. Started at 100 µM, it managed one phosphorylation cycle and stopped; topped back up to 1 mM, it promptly started cycling again.

Two phosphorylation sites mean that in principle a cycle needs only two ATP per KaiC. A 2015 analysis of the free-energy cost of accurate oscillations suggests the extra thirteen buy phase coherence: a steadier clock. A 2016 theorem says the same in general: precision has an energetic price, and an uncertainty ε costs at least 1/(10ε²) ATP. A clock driven from outside, by daylight for instance, can be precise almost for free, because the cost moves to whatever drives it.

Sources

Nakajima M. et al. 2005, Science 308:414-415, doi:10.1126/science.1108451
Terauchi K. et al. 2007, PNAS 104:16377-16381, doi:10.1073/pnas.0706292104
Cao Y., Wang H., Ouyang Q. & Tu Y. 2015, Nat. Phys. 11:772-778, doi:10.1038/nphys3412
Barato A. C. & Seifert U. 2016, Phys. Rev. X 6:041053, doi:10.1103/PhysRevX.6.041053
Abe J. et al. 2015, Science 349:312-316 (the slow ATPase)
Rust M. J. et al. 2011, Science 331:220-223, doi:10.1126/science.1197243

The interrogation room

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 KaiC clock protein

This is the photocopied wanted poster for KaiC clock protein, No. 138 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.