The Half Decent Pharmaceutical Chemistry Blog

Frankly, this is not the “scientific” post I thought I would have written before going on holiday, but real life has drawn my attention to a different subject: headphones. Although I haven’t begun packing yet, today I selected the headphones I will use while cycling (the main activity I’ll practice on this approaching holiday). Obviously I didn’t go for those Apple give you with the player as they are quite possibly the worst headphones I’ve ever seen.

To be frank with you, none of those I own, though, completely satisfies me: none of them, in fact, can be literally plugged in my ears. Actually I went to a shop to see how much in-ear headphones eventually cost. As it turned out, too much, at least considering the good ones (those that last more than, say, a year).

All this made me think of the role headphones play in our life. Vital, for what concerns me, as I’m not sure I could ride a bicycle without listening to music any more.
However, if you’re thinking that I’m the only headphones-iPod addict (or iPodaholic, still not sure which is the best expression), you’d probably ignore what Rad50 is. And if you do it, this means you know little about structural biology, as this protein is likely to be the best-known member of the outrageously famous ABC-ATPase superfamily.

This protein is, indeed, dramatically important: it repairs DNA double-strand breaks once it has dimerized, an event that occurs only in the presence of ATP. That’s due to a particular, striking feature of Rad50. Each monomer is formed by two lobes: one contains the Walker A sequence, while the latter the Walker B and the Signature Motif. ATP, however, binds to a site created by the Walker A and B of a monomer, whereas the Signature Motif comes from other one: this not only strengthens the interaction with ATP (as the distances are excellent for this purpose), but it also stabilizes the dimmer.
At this point you might be wondering what connection between headphones and such a protein one could possibly find. Well, the answer is simple: although structural biologists do not entirely agree on this matter, the most plausible dimerization model to date is the so-called single dimmer headphone one. According to this theory, the two globular heads of the dimmer would be very close to each other, when bound to ATP.
However, given that the protein dimerizes only in the presence of ATP, when this molecule is absent the two monomers really look like headphones: two globular heads, linked by a wire which, in this case, is a coiled coil. Each Rad50 monomer, in fact, presents an approximately 800 Å long tail: the two coils tightly wind around each other, strengthening the interaction between the monomers so that, even when ATP is missing, they are not really separated and can quickly rejoin to repair a damaged DNA.

What’s more a coiled coil is exactly how your earphones look like when you take your iPod out of your pocket, even if you had carefully and neatly wrapped them around the player. How frustrating is it?!