Protein · Lobeworks/17

A protein is a molecular machine made of a chain of amino acids folded into a precise three-dimensional shape, and in the brain proteins do nearly all the work: they are the channels, pumps, receptors, enzymes, transporters and scaffolds of every neuron, each doing its job because of its shape.

Protein. A protein is a molecular machine made of a chain of amino acids folded into a precise three-dimensional shape, and in the brain proteins do nearly all the work: they are the channels, pumps, receptors, enzymes, transporters and scaffolds of every neuron, each doing its job because of its shape.

A gene is read into messenger RNA and the ribosome strings amino acids in that order, choosing among twenty kinds with different side chains (charged, oily, small, bulky). The chain then folds: the oily side chains hide inside, the charged ones face the water, and the chain settles into the shape of lowest energy. Christian Anfinsen showed in the 1950s and 1960s that the enzyme ribonuclease, unfolded in a test tube, refolds by itself into its working form, so the sequence alone holds the information for the shape (Nobel Prize, 1972). That shape is the function: the pore of a sodium channel admits sodium because of the width and charges of its lining, a receptor binds its transmitter because the pocket fits it.

One letter can change the machine. A single swapped amino acid in a sodium channel can make it open too easily or not at all, which is how many genetic epilepsies begin.

Shapes can go wrong. Misfolded proteins can stick together into aggregates, and keeping proteins folded, repaired or destroyed is the work of proteostasis, whose failure marks Alzheimer's and Parkinson's diseases.

They are made, moved and replaced. A neuron builds many of its proteins in the cell body and ships them down the axon, and most are replaced over days to weeks, so a stable synapse is made of parts that keep changing.

The sequence decides the fold, and the fold decides the job.

Change one amino acid in the wrong place and a channel that should open on cue opens at the wrong time.

Questions: Why does one changed amino acid in a channel protein matter so much? Because the sequence decides the fold and the fold decides the job. A channel admits its ion through a pore whose width and charges come from the amino acids that line it, and opens on cue through parts that move when the voltage changes. Swap one amino acid in the wrong place and the pore or the gate changes shape: the channel may open too easily or not at all, which is how many genetic epilepsies begin.