Chapter 4 — Molecular Delivery

Kinesin is a molecular motor protein that walks. It moves along protein tracks called microtubules inside every living cell, carrying molecular cargo from one location to another. When visualized, its motion is indistinguishable from bipedal walking—two protein domains alternate stepping forward in a hand-over-hand mechanism, each step exactly 8 nanometers long, corresponding to the spacing between tubulin subunits in the microtubule track.

Kinesin powers transport of organelles, vesicles, chromosomes, and signaling molecules throughout the cell interior. Neurons depend on it critically: a single motor neuron axon can extend a meter in length, and every molecule required at the synaptic terminal must be transported from the cell body. Without kinesin the synapse degrades; without intact synapses neural transmission fails.

Kinesin was identified in 1985 by Ronald Vale, Thomas Reese, and Michael Sheetz. The crystal structure was solved by Kull and colleagues in 1996. The walking mechanism, confirmed by single-molecule experiments, requires the precise geometry of the motor domains, the microtubule track, and the ATP hydrolysis cycle to be coordinated at the nanometer scale. No component of this system provides transport function without the others.

Vale, R.D., Reese, T.S., Sheetz, M.P. "Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility." Cell 42, no. 1 (1985): 39–50. Kull, F.J. et al. "Crystal structure of the kinesin motor domain reveals a structural similarity to myosin." Nature 380 (1996): 550–555.

Chapter 5 — The Clot That Cannot Fail

When a blood vessel is cut, a cascade of more than twenty proteins fires in a precise, ordered sequence to form a clot. The margin between outcome states is absolute: too little clotting and the organism bleeds to death; too much and it dies of thrombosis. The system regulating this margin consists of activators and inhibitors that must all be present and calibrated before any injury occurs.

The cascade works like a molecular relay race. Each protein is activated by the preceding one and activates the next. Final steps convert fibrinogen to fibrin, forming the structural meshwork of the clot. Platelets are recruited. Inhibitory signals localize the clot to the damage site. When healing is complete a separate fibrinolytic system dissolves the clot.

Behe documented the irreducible complexity of the clotting cascade in Darwin's Black Box. Every functional intermediate in any evolutionary development of this system would be lethal: insufficient clotting kills as surely as absent clotting. There is no functional, non-lethal stepping-stone pathway through a cascade where every incomplete version either fails to stop bleeding or kills the organism by clotting it.

Behe, M.J. Darwin's Black Box. Free Press, 1996. Chapter 4. Davie, E.W. and Ratnoff, O.D. "Waterfall sequence for intrinsic blood clotting." Science 145 (1964): 1310–1312.