Saturday, July 17, 2010

Protein Folding

Medical Meanderings 4 November 2009

Know When To Fold ‘Em ©

“The Universe is not only stranger than we imagine, it is stranger than we can imagine.”
J. B. S. Haldane (1892-1964)

If a mad scientist were to want to create a living human cell (and some non-mad scientists are working on this), he (women rarely become mad scientists) could not simply pour all the chemical ingredients into a blender and expect a good result. Most biological chemical reactions are so slow that they essentially don’t happen at all on their own. How do our own cells, then, manage to coax these molecules to react, thereby staying alive and keeping us alive?

The answer is the miracle of proteins. Every one of our cells contain millions of different proteins, which are the most versatile molecules known, the multi-function Swiss Army knives of biology. One class of proteins, called enzymes, are responsible for taking two different molecules and marrying them in the chemical reactions needed to maintain life. Enzymes are so efficient in this role as catalysts that they can increase the rate of a chemical reaction a billion- or trillion-fold. Each enzyme has a small pocket into which specific molecules fit snugly, like a plug into a socket, allowing the enzyme to do its chemical work.

What allows an enzyme to use this kind of key-in-lock specificity? Every protein is made of a long chain of building blocks called amino acids, which are linked together, like a string of pearls, in a particular order determined by a length of DNA. The chain of amino acids is called the “primary structure” of a protein. However, amino acids have positive and negative charges, so we can imagine a string of magnetic pearls which, far from hanging simply around a graceful neck, would stick to each other according to the rules of magnetic attraction. Amino acid chains tend to morph into spirals or crinkled sheets called the protein’s “secondary structure.” The sheets and spirals then bend sharply, stick together, fold into each other. All this folding and bending results in the protein’s “tertiary structure,” a specific three-dimensional shape, more complicated than paper origami, which determines the function of the protein enzyme.

Now we can see why a change (mutation) in a particular gene might have major effects in the body. The DNA sequence of the gene decides the order of amino acid building blocks, but if even a single pearl is changed, the string folds up in a completely different way, and that enzyme will function very differently. The lock changes, and maybe the key fits better, maybe it doesn’t fit at all. Depending on the protein, the change can be helpful, neutral or catastrophic.

Scientists are beginning to better understand the effects of protein folding on the development of embryos, various diseases (such as “mad cow” disease and sickle cell anemia) and the overall course evolution has taken. The complicated path from gene to amino acid to protein folding is becoming clearer, and it will be exciting to see how the future...unfolds.

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