X-ray crystallography (for laymen)

While I love explaining things, explaining what is x-ray crystallography over lunch proves to be too difficult. Hence, I have decided to write a short post to explain what is protein crystallography as simple and clear as I can.

First, what are proteins? I know the picture of chicken drumstick will appear in your mind right now, but please think small, really small. The chicken drumstick you eat contains a lot of proteins, which will be digested in the body and will be reused to make new proteins that our body needs. Proteins are made of smaller components called amino acids. You could think of the small amino acids are like LEGO bricks, and a protein is like a LEGO house built using those bricks. It is amazing how many kinds of houses these bricks can build! And our body is like a big city that contains skyscrapers, underground tunnels, hospitals, and schools.

Now, say that a bad guy appeared and start robbing the residential area. The police want to arrest the bad guy but no one knows how he looks like. To see what the bad guy looks like, we will take a photograph of him. The photo can be used to warn the residents, and help the police to arrest the bad guy. The photo also allows the experts to develop a special weapon that captures only the bad guys.

In this story, the bad guy is a protein from bacteria or viruses, the police are the immune system, and the photograph is the crystal structure of the protein. Warning the residents is like having a vaccine, and the special weapon is like an antibiotic or antibody drug.

By now I hope you see the importance of having a crystal structure of a protein. Unlike a typical bad guy, which ranges around 1-2 meters, the protein is much smaller, around 10-100nm, which is 0.0000001 meter! It’s still 1000x thinner than the thickness of your hair.

So, how can anyone see it? How about using a microscope? For your information, the wavelength of a blue light is 450nm. This means typical proteins are way too small to be spotted under the microscope.

The picture on the right is a typical protein structure. Purple coils are called alpha helices and yellow ribbons are called beta sheets.

 

What if we can produce a lot of the same protein, pack tens of thousands of them very closely into a huge formation? Sounds like a crowd CG effect commonly used in modern movies. These proteins, after being packed into a regular formation, will form crystals in the “right” condition. So, how do we know what condition is the right condition? The answer is we don’t! We have libraries of conditions that have a high likelihood of making the proteins to form crystals, but there are literally thousands of conditions to try. Getting a protein crystal requires a brute force trial-and-error effort similar how Thomas Edison went through thousands of prototypes before finally invented The light bulb.

A protein crystal is around 100 micrometers long, and there are a variety of shapes that come with it. For example, this is one of my crystals (which by the way, obtained after about 1000 conditions tried):

After obtaining a beautiful crystal, we shoot intense X-ray beam onto the crystal. The resulting shadow (diffraction pattern) can be used to calculate the structure of the protein (after Fourier transforms and other rather advance mathematics).

Now let’s go catch some bad guys and save the world!