Easier Way to Convert Proteins into Crystals

Roland Piquepaille writes "As you might know, proteins need to be transformed into 3-D crystals before their atomic structures and their properties can be analyzed. And production of high quality crystals from proteins has been a difficult task until now. But scientists in the U.K. have successfully used a porous medium, or 'nucleant,' a material that encourages protein molecules to crystallize. Their first step towards 'holy grail' of crystallography could help speed up the development of new medicines and treatments."

This is Big

[eldavojohn]

Ok, so I don't know a ton about nuclear medicine, I know just enough to be dangerous. Protein crystallization allows us to see it's structure [davidson.edu] whereby we better understand its function [faseb.org].

The reason this bit of news is so big is that it will (hopefully) allow researchers a way to quickly look at the structures of proteins in such as (in the second link) infectious diseases transmitted by prions, or protein particles. Prions seem to be pure protein; they contain neither DNA nor RNA.

If we can understand the shape and formation of proteins, we can understand how viruses and cells work because proteins are the building blocks. Viruses are obviously first on the chopping block as they are the smallest and infect millions of people world wide (AIDS, influenza, the common cold, etc.).

Re:An Even Easier Way to Convert Proteins to Cryst

[napalmfires]

http://en.wikipedia.org/wiki/Urine [wikipedia.org] Urine doesn't have protein in it...

Re:This is Big

[ruckerz2k]

Though the parent is correct, this technology greatly reduces the time and effort involved in 'crystallizing' proteins. Most common approach is to use the hanging drop method [davidson.edu], where a drop of the sample is suspended over a highly concentrated solution. The sample concentrates due to the negative osmotic pressure and the protein 'crystallizes'. The crystallization process can be hastened by using a 'nucleant', usually a small crystal of the sample that you have previously crystallized. Also, the exact identity and composition of the concentrated solution is varied in order to find the right crystallization conditions. This is a very tedious process (imagine setting up 96 different concentrated solutions, each differing in about 1% concentration of the solutes) and time intensive.

The discovery of a 'universal' nucleant (close to the one suggested by the authors of this study) and the development of a matrix to encourage crystallization would greatly speed the screening process, and ultimately, crystallization of proteins.

Understanding protein structure..

[jonasmit]

is critical to translating the information obtained in, for example, the Human Genome Project. The DNA gives us the blueprint but the protein does the work. Currently, there is no way to predict protein structure from DNA. Therefore, you must see the structure to understand how the protein works. Also it is important to note that in Protein-Protein interactions. Protein-Protein interactions are important in normal cell singalling events as well as in how virii infect cells (like HIV1 binding to gp120/gp41).

Re:W00t!

[Red Flayer]

Did you check the submitter link? rel=nofollow. Maybe if you'd read the commments by Taco in last weeks /.metaarticle, you'd see why.

Roland Piquepaille knows nothing.

[Anonymous Coward]

Roland Piquepaille writes "As you might know, proteins need to be transformed into 3-D crystals before their atomic structures and their properties can be analyzed.

Simply NOT TRUE.

Proteins must be crystalized before they can be analyzed by X-ray crystallography. They can be analyzed by many, many other methods even if they aren't crystals. And frankly, given that proteins aren't in crystalline form in the body, knowing the crystalline form isn't always useful.

NMR (nuclear magnetic resonance) spectroscopy will elucidate the stucture of a protein in solution, which is normally far more useful.

Aside from chemists, biologists & MDs, most people (including paparazzi like Roland)haven't heard of NMR.

Re:This is Big

[SIGFPE]

Talk about Karma whoring! A bunch of sentences culled from a variety of sources from someone who really doesn't know what they are talking about. Now that's dangerous.

Viruses are obviously first on the chopping block...

Non "obviously" at all. There are countless medical applications for X-ray crystallography. Any time you want to study the structure of a protein it comes in handy. Many diseases are attacked by researchers from the point of view of receptor binding - the binding together of proteins to other compounds like a lock and key. Such receptors act like switches activating or controlling biological processes. These are ubiquitous in nature and understanding the shape of these 'locks' and 'keys' can be useful in trying to understand the mechanisms of all kinds of diseases whether or not they are caused by pathogens.

Re:This is Not so Big

[sam_handelman]

This is an improvement on a known technique. The abstract [pnas.org] is as over-reaching as the press release (the linked article).

  I'm not a crystallographer, but I work in a lab group that has many crystalographers in it.

  It's been known for some time that you can use a variety of materials - including things with porous surfaces, which is what is used here - to assist the process of crystallization. Crystalization is difficult and, frankly, rather unscientific - you take the protein you want to crystallize, and you try different techniques and tricks (of which porous nucleants are an example) until you can get it to work.

  So, okay, it would be a "holy grail" if you could find one technique that would let you crystallize most things without going through all that trouble.

  However, based on only seven examples (Subscribers only, I'm afraid. [pnas.org]), you absolutely cannot conclude that this is a universal nucleant - based on the similarity among the seven examples, I'd be very surprised if it were; even if it were a universal nucleant, nucleation does not always guarantee usable crystals.

  Those caveats aside, it does look like a useful advance.

Re:Ever hear of NMR structure determination?

[Red Flayer]

NMR diesn't rquire crystallization, but it does require transfer of the protein to a non-native solution (which may affect tert structure). Not that crystallization doesn't do this also...

Plus, NMR results or more vague than X-Ray crystallography, and can only be used with small proteins, whereas crystallography works for even very large proteins (provided you can get them crystallized).

Re:Ever hear of NMR structure determination?

[Bowling Moses]

The molecular weight limit of NMR has been increasing quite a bit and now proteins on the order of 100 kDa are possible, although technically challenging. Lewis Kay's group at the University of Toronto has done a solution structure of an 80 kDa protein, for instance.

I don't know a ton about nuclear medicine.

[Anon.Pedant]

Quibble #1: This is not "nuclear medicine", it is "structural biochemistry."
The field of nuclear medicine is concerned with things like radiation therapy and PET scanning.

          http://science.howstuffworks.com/nuclear-medicine. htm [howstuffworks.com]
          http://jnm.snmjournals.org/ [snmjournals.org]
          http://www.biomedcentral.com/bmcnuclmed/ [biomedcentral.com]

Quibble #2: Your second link is very outdated. Structures for several prion proteins were determined several years ago, using both X-ray diffraction and NMR methods. Science moves on, but many webpages are never updated.

Re:Sounds Like A Lot Of People Here Are Really Sma

[SyvanX]

I've thought about this plenty, but to have some benchmarks for the shapes different proteins make, we need lots of evidence that a folding model matches the true output of the mRNA. So yeah, I look forward to the day when we can truly predict how they fold, but it's going to take a lot of work to determine the ways that different amino acids interact and how the conformational shape changes due to different interactions throughout the process of elongation. Then if that wasn't enough, we'll need to also account for the different molecular chaperones that assist some proteins in finding a functional conformational structure. I'd like to see some of the Bioinformatics guys get into this type of research (if they're not already), I'm sure there's a brilliant Biochemist out there just waiting to team up with a programmer to create a simulation that can accurately fold any sequence of amino acids.