Tuesday, September 27, 2005

but what would you change if you could?

This class is going to be the end of me, I tell you. I try to speak intelligently with the instructors, and I get all tongue-tied and twisted, just an earthbound misfit, I. Seriously- I am worried that I am just going to blurt out "I lurve you!" instead of talking about the articles I am researching for class. I left class last night flushed over chatting about RNA. Not good. This class is turning me into a friggin' sixteen-year old. And you know what? I kind of like it.

In days of yore, there was some thought that protein binding had almost everything to do with finding the right fit. In enzymes, this is known as the lock and key hypothesis. I won't bore you with all the details, but it supposes that a protein just has this void, this part of itself that it is yearning to find, and that's how it ultimately binds its specific substrate. Much like a lock and key fit together. Or like a hook and an eye.

Since then, layers and layers of complexity have been added to that initial model. It turns out that proteins are just fine on their own, and are not necessarily holding still, arms spread, waiting. What is more, it's not about a perfect fit. It is more to do with a series of perfect interactions. Proteins don't fuse (most of the time); they bind. The essential components of their individual parts remain the same. But the right part of a protein will come in contact with the right part of another protein's receptor, and the right interactions will trigger binding. And binding itself is a complex process. The right interactions induce the proteins to change their conformations just so, so that they fit together. And a bound protein quite often has a completely different shape/conformation than the same protein, in its unbound state, does.

These conformational changes, in general, are fascinating. Okay, to me, they are fascinating. "Oh," she says, "You're changing." But we're always changing. I mean, the idea that every interaction we have changes us in some way is not just amazing- it has to be true. It is why I rarely look back on things with regret- if you change one thing that happened, you disrupt the whole process of how you got to where you are now, who you are now.

A wrinkle in this notion, an idea that is a bit gloomy, is that a protein can have certain interactions, interactions outside of its binding area (or active site for you nomenclature junkies). Some of these interactions can trigger a conformational change that will render the protein inactive, unable to further bind anything. Something has happened, and the protein is closed for business. Movies have been made about this, but they always assume that the inactivity is reversible, that you can change back to your original conformation. I remain uncertain.

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