Protein Pirouettes: Part 1

Ezetimibe
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How to Dance Like a Protein: Part 1

Ezetimibe
Pirouettes performed by the target protein of the drug ezetimibe, a medication used to lower cholesterol (a).

Proteins—the practically invisible, molecular dancers that serve as the faithful building blocks of me and you. Yes, it is true that even dancers are made of dancers, and proteins perform some of the most amazing dancing of all by way of folding. Protein folding is actually a lot like belly dancing, with all of its vibrations and shimmying.

Now, I am not—by any leap of the imagination—a dancer, but I do happen to know a lot about nature’s smallest dancers of all. Perhaps you can find some inspiration in learning about our nanoscopic friends, and learn about the science of protein folding along the way!

Butterfly Protein
The humble butterfly protein. Or two chicken legs pressed together? Choose your own adventure (b).

A reason to dance. What, you think that the protein above woke up looking that beautiful? To understand how and why a protein folds, it’s important to remind ourselves of how they come to exist in the first place—the central dogma of molecular biology. DNA is transcribed into mRNA, and mRNA is translated in proteins. That probably sounds like an awful lot of alphabet soup, but let’s simplify things with an analogy: your cell is a small company called Cell Incorporated®. Every company needs a CEO to boss everybody around, and that’s “DNA” (deoxyribonucleic acid), whose office is located in the center (nucleus) of Cell Inc.®. However, even a visionary leader is powerless if they cannot communicate that vision, so they employ messengers called “mRNA” (messenger ribonucleic acid). Now, the company needs to produce something to make a profit, and that product is called “proteins.” Ergo, the central dogma of molecular biology: DNA -> mRNA -> proteins.

To make their product, Cell Inc.® needs raw materials—these are chemicals called amino acids, the steel from which proteins are made. As a protein is being constructed (or translated from the “language” of nucleic acids to amino acids), it is formed piece by piece in a long chain. Imagine that every component that makes up a cell phone was attached to one another by a tiny string; if you laid out that string, it would look nothing like a cell phone (let alone work like one), and the same is true for proteins. Unfortunately for them, cells don’t have the benefit of assembly lines and blue collar workers; therefore, the product must put itself together.

Understand the immense difficulty of this task for a moment: Cell Inc.® needs to make a product out of steel blocks connected by string that, due to the unique properties of each block, will self-assemble into something useful, something beautiful (cell phones are beautiful, okay?).

Wow.

Fortunately for them, however, cells possess the most powerful allies in the entire universe: the laws of physics (c). And it is these laws that govern what is possible, what is probable, and what isn’t. Using physics, Cell Inc.® came up with a solution to make its products self-assemble—to make the pieces of the protein fold nicely together: they dance.

Dancing with purpose. There, I said it: protein folding is dancing. Proteins jiggle, wiggle, twist, and turn, always moving, vibrating, and colliding with themselves and anything else around. Although the motions may be random, the dance itself is done with an immense sense of purpose, guided by the very nature of the protein itself. From chaos and entropy, proteins allow their amino acid bodies to guide their movements towards the native structure, the final, functional form of proteins that we’re familiar with (see the image above). From the very moment that a protein is born, it begins to fold—dancing, you might say, is an integral part of the nature of what it means to be a protein.

There’s an important life lesson to be learned from the humble protein, here. We should allow our natural talents and capabilities to guide our decisions, rather than force upon ourselves choices that deviate from the desires of our hearts. In the early moments of a protein’s birth, it seems impossible to foresee anything of worth or interest arising from a tangled mess of amino acids slapped together, moving erratically in the dark loneliness of a cell. However, perhaps if we live our lives like a protein—following our hearts, listening to our bodies, and maybe even a little dancing—we can find fulfillment, and become the best, most beautiful version of ourselves that we can be.

You do you, aquaporin. You do you (d).

To learn more about proteins, check out my second article here. I’ll be exploring protein folding in greater detail, and discuss how even one false move on the dance floor can transform an otherwise contributing member of cellular society into a murderer.

—Cooper

TL;DR:

  • Proteins are made up of amino acids
  • Central dogma of molecular biology: DNA -> mRNA -> proteins
  • During and after translation, proteins must fold to become functional
  • Protein folding happens as a consequence of the protein’s inherent chemical structure

Notes

(a) Adapted, surface structure of human NPC1L1 (3QNT) visualized in NGL. (1-2)

(b) Adapted, surface structure of human DNA topoisomerase IIa ATPase/ADP (1ZXN) visualized in NGL. (1-2)

(c) This is ultimately where biochemistry comes from; biochemistry is the study of biological chemicals, chemistry is the study of chemicals and how they interact, and those interactions are governed by the law of physics. Biochemistry is basically biological chemical physics. The laws of physics, as they apply to biological chemicals (biochemistry), govern the movements and interactions of proteins (which are also biological chemicals, albeit bigger ones)—just as they govern the movements and interactions of us.

(d) Adapted, surface structure of bioassembled human aquaporin (4CSK) visualized in NGL. (1-2)

References

(1) AS Rose, AR Bradley, Y Valasatava, JM Duarte, A Prlić and PW Rose. Web-based molecular graphics for large complexes. ACM Proceedings of the 21st International Conference on Web3D Technology (Web3D ’16): 185-186, 2016. doi:10.1145/2945292.2945324.

(2) AS Rose and PW Hildebrand. NGL Viewer: a web application for molecular visualization. Nucl Acids Res (1 July 2015) 43 (W1): W576-W579 first published online April 29, 2015. doi:10.1093/nar/gkv402.

Part 2 coming soon!

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Welcome To Poise and Potions!
Where Art and Medicine Dance
We hope to be your go-to blog for all things art, medicine, and everything in between