The Mysterious Art of Protein Origami

Name:Mrs. Zuccarelli

Date:Biology

The Mysterious Art of Protein Origami

M. B. Cox

Reading Prompts: Please produce a thorough response to the indicated prompts below. This should be written as an ESSAY discussing the prompts, not as short blurb answers referencing the prompts. Essentially you are writing a review (summary + reflection) of the assigned reading.

Describe several insights you’ve gained from your reading.
Describe the four levels of protein structure and how proteins relate to origami.
Provide examples of proteins and describe their specific functions.
CREATE – Follow the instructions in the attached PDF and create a protein!

Title:The Mysterious art of protein origami: a puzzle for the next generation of biologists

Author(s):Mary Beth Cox

Source:Odyssey.23.1 (Jan. 2014): p44.FromScience In Context.

Document Type:Article

Full Text:

Origami is the paper-folding art. It starts with a flat sheet of paper. A careful crease is made here, then another fold there, and presto! The flat sheet is magically transformed into a 3-D object like a hat, or a boat, or a swan. Now believe it or not, another kind of origami is going on all the time inside the cells that make up the bodies of living things. Obviously a whole sheet of paper can't fit into a tiny cell (no matter how many times the paper has been folded). Small-scale origami is done instead with molecule-sized strands of amino acids. Straight amino acid strands fold up into three- dimensional proteins. How do microscopic proteins perform this transformation? No one knows. It's a scientific mystery.

What Are Proteins?

That proteins are at the center of a mystery is a bit ironic. Proteins themselves aren't all that mysterious. As a group, they are homely, hard-working biomolecules. DNA is a much more shadowy molecule, given its frequent association with crime scenes. Proteins don t have time for such nonsense. They're preoccupied with the everyday business of life. There are prominent participants in all sorts of biological processes.

Proteins called enzymes drive the chemical reactions going on inside living things. Transport proteins like hemoglobin take other molecules where they need to go. Hormones are proteins that regulate and coordinate bodily functions. Antibodies protect against infectious microbes. Collagen and keratin provide structural support. Muscle fibers contract to bring about motion. Receptor proteins keep cells informed about the conditions in their immediate surroundings.

It's also odd that protein folding is such a mystery when other steps of protein production are so well understood. As any biology student knows, textbooks describe in exhausting detail how cells make amino acid strands. Here, briefly, are the highlights: Protein synthesis starts with a cell's DNA. DNA is a database with stored instructions for making proteins. The instructions are copied from DNA to another biomolecule called RNA. RNA carries the instructions to a cellular structure called a ribosome. Amino acids are fetched to the ribosome and joined in the correct sequence as per the instructions. Usually that's where the textbook description of protein synthesis ends. But if proteins were nothing more than strung- together amino acids, they'd be about as useful as a wet noodle.

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There's Work to Do!

A protein can only do its work if it folds into a proper three-dimensional shape. That's not surprising, really. A flat sheet of paper doesn't function very well as a hat or a boat unless it undergoes an origami transformation. Proteins do their various jobs by interacting with specific targets. A digestive enzyme interacts with the nutrient it is supposed to break down. An antibody interacts with a germ.

A protein molecule's 3-D shape is absolutely critical for a successful interaction. Because of this, proteins and their targets are often compared to locks and keys. Locks and their keys interact in a useful way because their 3-D shapes are a perfect match. It's likewise for proteins and their intended targets.

So what happens if a protein doesn't fold into the right shape? At best, a misshaped protein is ineffective at its job. At worst, a serious problem ensues. Cystic fibrosis (CF) is an inherited disorder that's characterized by a buildup of thick, clogging mucus in the lungs. CF is caused by the improper folding of a protein in the membranes of cells. Both Alzheimer's disease and Parkinson's disease involve misfolded proteins in the tissues of the brain.

Certain cancers are associated with a misfolded protein that normally would suppress the formation of tumors.

Tracking the Clues

Protein folding is obviously an important matter. It's also an entertaining challenge. Protein specialists, like most scientists, love a good mystery. They have already spent years investigating the unknowns of protein folding. Their research has uncovered some tantalizing clues.

They've discovered that freshly made amino acid strands fold up immediately after synthesis. Somehow, the sequence of amino acids in a strand dictates the final folded shape of a protein. Folding requires multiple steps. Coils, pleats, and other intermediate shapes form first. Then these are arranged into a final shape such as an elongated fiber or a spherical glob. Folding is helped along by so- called chaperone proteins. It's the job of these specialized proteins to help other proteins fold up properly. As if proteins didn't already have enough work to do!

Despite all of the investigative effort, no one has identified a fundamental set of protein folding rules. There is no such thing as a handy illustrated step-by-step guide for the art of protein origami. Too many key questions are still unanswered. How does a protein fold so quickly-after the synthesis of its amino acid strand? How does each protein choose the one correct way to fold given seemingly countless possibilities? How does a protein fold with exacting precision inside a crowded cell that's chock-full of many other busy molecules?

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Young Scientists, You're Up!

When will the mystery of protein folding finally be solved? Optimistic researchers think the answer to that question is: Soon. At present, computers loaded with molecular modeling software can accurately simulate the folding of a few very small proteins. With hard work, patience, and a little luck, the next generation of researchers will likely expose the last stubborn secrets of protein folding. The benefits from their work will be far-reaching. Diseases caused by improperly folded proteins will be better understood. Perhaps there will be improved treatments or even cures. It will become possible to predict the three-dimensional shape of proteins from their amino acid sequences. This may lead to the design of artificial amino acid strands that automatically fold into helpful biologically active objects. If so, then those future designers won't just be scientists--they will be protein origami artists, too.

Amino acids--Small molecules that Join in a chain to make up proteins

Prion--A protein that causes an infectious disease

Caption: A key fits into a lock because their shapes are a perfect match. A three-dimensional proteins fits its target like the right key in a lock. But what if the shapes don't match? You're locked out, or you're in biological trouble!

Caption: Mad cow disease is caused, at least in part, by a protein called a prion. Prions ire notorious troublemakers. They invade healthy cells and encourage otherwise well-behaved proteins to fold incorrectly.

Seeing Protein Folding in Action

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This supercomputer simulation shows the unfolding of a protein (rhodanese) by a chaperone molecule.

The protein is red. The chaperone molecule is blue, yellow, green, and orange.

Simulations like this may help identify treatments for diseases caused by incorrectly folded proteins.

The study of protein folding is known as molecular dynameomics.

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FOLDIT: The Protein Folding Game: FOLDIT IS AN ONLINE PUZZLE GAME offered by the Center for Game Science and the Department of Biochemistry at the University of Washington. Citizen scientists are awarded high scores for folding proteins of interest into low-energy shapes. In 2011, gamers helped to determine the correct 3-D structure of a viral protein that is important in the battle against AIDS.

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For an introductory video, search "welcome to Foldit!!" on YouTube. Or check out the official Foldit site at

Another Protein Mystery

PROTEINS PARTICIPATE IN THE PRODUCTION new DNA molecules. The process is called replication. DNA's instructions are copied in order to synthesize new amino acid strands. That process is called transcription. Proteins are needed to make new DNA. DNA is needed to make new proteins. How did this situation come about? Did one of these molecules appear in Earth's living creatures before the other? Or did these two complex molecules A evolve simultaneously? It's a chicken-or-egg kind of mystery ...

Cox, Mary Beth

Source Citation (MLA 7thEdition)

Cox, Mary Beth. "The Mysterious art of protein origami: a puzzle for the next generation of biologists."OdysseyJan. 2014: 44+.PowerSearch. Web. 19 Nov. 2015.

URL

Gale Document Number:GALE|A358630158