Tag Archives: Alpha helix dimensions

A molecular ruler

Time to cleanse your mind by leaving the contentious world of social issues and entering the realm of pure thought with some elegant chemistry.

You are asked to construct a molecular ruler with a persistence length of 150 Angstroms.

Hint #1: use a protein

Hint #2; use alpha helices

Spoiler alert — nature got there first.

The ruler was constructed and used in an interesting paper on CAMP nanoDomains (about which more on the next post).

It’s been around since 2011 [ Proc. Natl. Acad. Sci. vol. 108 pp. 20467 – 20472 ’11 ] and I’m embarrassed to admit I’d never heard of it.

It’s basically a run of 4 negatively charged amino acids (glutamic acid or aspartic acid) followed by a run of 4 positively charged amino acids (lysine, arginine). This is a naturally occurring motif found in a variety of species.

My initial (incorrect) thought was that this couldn’t work as the 4 positively charged amino acids would bend at the end and bind to the 4 negatively charged ones. This can’t work even if you make the peptide chain planar, as the positive charges would alternate sides on the planar peptide backbone.

Recall that there are 3.5 amino acids/turn of the alpha helix, meaning that between a run of 4 Glutamic acid/Aspartic acids and an adjacent run of 4 lysines/arginines, an ionic bond is certain to form between the side chains (and not between adjacent amino acids on the backbone, but probably one 3 or 4 amino acids away)

Since a complete turn of the alpha helix is only 5.4 Angstroms, a persistence length of 150 means about 28 turns of the helix using 28 * 3.5 = 98 amino acids or about 12 blocks of ++++—- charged amino acids.

The beauty of the technique is that by starting with an 8 amino acid ++++—- block, you can add length to your ruler in 12 Angstrom increments. This is exactly what Cell vol. 182 pp. 1519 – 1530 ’20 did. But that’s for the next post.