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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."
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 whereby we better understand its function.
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.).
My work here is dung.
Drink lots of beer and then pee in the snow.
He who knows best knows how little he knows. - Thomas Jefferson
CURSES!
They've beaten me to the protein-to-crystal technology that was to be the core of my patent-pending Doomsday Device!
I wonder what the DeathLegion's union rep will say when I announce 10,000 layoffs...
Reality has a conservative bias: it conserves mass, energy, momentum...
...using Kleenex for the nucleation process.
http://en.wikipedia.org/wiki/Urine Urine doesn't have protein in it...
Roland Piquepaille's article not linked to his blog outside of the "credit link"? I wonder, did Roland make a mistake or maybe Scuttlemonkey read my post?
45 5F E1 04 22 CA 29 C4 93 3F 95 05 2B 79 2A B2
does beer? I think that's what was meant.. beer -> snow
A guilty conscience means at least you've got one.
By speeding up the (currently extremely tedious) process of crystallization and hopefully making inroads into the ~70% of all protein which currently can't be crystallized, this will rapidly improve our understanding of the structures of whole classes of proteins.
---If you can't trust a nerd, who can you trust?
-------------------- CUT HERE --------------------
Everything above this line are lame jokes from people who couldn't be bothered to read the article.
I thought the jokes were kind of funny
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).
To find the three-d structure by x-ray crystallography, you have to crystallize the protein. Actually doing so, with different proteins, is an astoundingly difficult task, so much so that something like five Nobel prizes have been given for research into crystallization and x-ray crystallography development, and another ten or so Nobels given for determination of three-d structure of various proteins were, in essence, awarded for getting the protein to crystallize.
Side story: there was a famous German chemist named Emil Fischer, who originally determined the structures of a bunch of sugars. That was, again, largely a crystallization problem. He had, as Germans did in the 1890's, an enormous beard, and was playing with chemicals all day long, which tended to condense in his beard. It was said that if you could not get something to crystallize out of solution, no matter what you did, you asked Fischer to come to your lab and fluff his beard over your beaker, and the seed crystals falling from it were of such variety that one was almost guaranteed to be correct for your particular situation and get it to crystallize. So this isn't exactly NEW technology.
Nostalgia's not what it used to be.
Hopefully this will encourage more individuals to pursue advanced degrees in protein crystallography. I was recently at a talk where a soon-to-be PhD was discussing her crystallography work. She said that many people choose to pursue other areas in biochemistry/structural biology because protein crystallography is very unpredictable. Some proteins will crystallize in months while others can take YEARS! Waiting years before you can really dive into your PhD research is very discouraging.
well, at least it isnt Beatles-Beatles.
The war with islam is a war on the beast
The war on terror is a war for peace
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.
Unless the urinator has kidney damage!
As you might know, proteins need to be transformed into 3-D crystals before their atomic structures and their properties can be analyzed.
I knew that.
Urine SHOULDN'T have protein in it.
This is an improvement on a known technique. The abstract 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.), 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.
The good and new comes from no quarter where it is looked for, and is always something different from what is expected.
It does if you are sufficiently sick. (link pulled off of google but it makes the point.)
That said, even if you do have peptides in your urine, they don't crystallize when it hits the snow.
The good and new comes from no quarter where it is looked for, and is always something different from what is expected.
Why is this Smart Ass comment, modded up 3 as Insightful? WhiskeyTangoFoxtrot? Maybe modded to 2 as funny. MAYBE.
Sure being able to find suitable crystallization conditions for proteins is a bottleneck at the moment and this will aid in the process and add to the 20,000 plus know Protein structures, however, this is limited to certain types of proteins. A lot of really interesting proteins however are more flexible, and its this flexibility thats the key to understanding a lot of protein function. Structures derived from crystals don't give so much information about protein dynamics and molten globule like states of proteins, in fact when you crystallize proteins they tend to be locked into one conformation. Everyone in the field should keep this in mind always. A protein structure derived from a crystal structure is just a framework, its not a final representation of final function. More clues about this kind of information can be derived from NMR (Nuclear Magnetic Resonance), however the use of NMR is restricted to relatively small proteins. This is going to help, but its not huge, the real breakthrough will come when we can model any given protein sequence on a computer and have an acurate predicated 3 diminsional structure together with it molecular motions and dynamics in real time. Glad to see /. covering the field, its huge and its just started, we're at the begining of an exponential curve. Maybe /. should make a seperate section for this, I'd certainly be interested in contributing articles and news to such an effort.
The brilliance of x-ray sources are right now undergoing a revolution much faster than Moore's law.
Any sufficiently advanced libertarian utopia is indistinguishable from government.
IAASB (structural biologist), and while I can't verify their findings, I can back up the premise in the article that generating diffraction-quality protein crystals is one of the two major bottlenecks to X-ray crystallography (the other being purification).
It's pretty easy to understand why. Not only do you need pure protein, but one must find conditions under which that protein forms relatively large, single crystals. The chief variables, aside from the homogeneity of the protein you're starting off with, include temperature, pH, protein concentration, choice of and concentration of precipitant (generally a chemical that drives the protein out of solution), choice of and concentration of additive compounds, in some cases detergents... The researcher must traverse this multidemensional search space by trial and error, with a limited quantity of protein, looking for the optimal conditions. On top of that, the conditions that confer the ideal level of nucleation may not be ideal for crystal growth...
We have developed shortcuts over the past 20 years, or so. Kits are available that allow one to screen through frequently successful crystallization conditions. The number of conditions one can test in one go is gradually increasing, as things miniturize somewhat.
The ease-of-crystallization varies amazingly from one protein to another, and tricks that improve one do not necessarily work for another, but anything that simplifies the process will be greatly appreciated by the field.
The angel in the oatmeal.
Normal urine has proteins indeed:
"Hyaline Casts
These casts are the most common type of cast, and often they can be found in normal urine samples, especially after vigorous exercise. Hyaline casts result from the solidification of Tamm-Horsfall protein, which is secreted by renal tubular cells and may be seen without significant or abnormal proteinuria."
Quibble #1: This is not "nuclear medicine", it is "structural biochemistry."
. htm
The field of nuclear medicine is concerned with things like radiation therapy and PET scanning.
http://science.howstuffworks.com/nuclear-medicine
http://jnm.snmjournals.org/
http://www.biomedcentral.com/bmcnuclmed/
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.
I observe this phenomenon all the time on top of my uncleaned plates in the kitchen sink :)
between burial, cremation, or crystilization?
cool..
every day http://en.wikipedia.org/wiki/Special:Random
since beer doesnt have protein (enough to mention if it does) a more appropriate method would be to eat a high-protein mexican diet, then go visit the snow... it would be about the same constistancy
I hope this comes to market soon, because determining the crystallization conditions of a new protein, protein - protein complexes or, protein - nucleic acid complexes is the most difficult part of structure determination. However, there are many protein - protein complexes that don't form regular complexes, that is the same proteins can bind to different parts of its binding partner protein. I wonder if their new material works with such proteins. Ohh and here's the link to the full article made available by nyud.net for those who don't have PNAS subscriptions from their uni's:
Experiment and theory for heterogeneous nucleation of protein crystals in a porous medium
In a related story, the university has built a town for residents to move into and a modest price.
Yep. Three and four bedroom homes that do not have transmutation circles covered up with wallpaper. Oh, and pay no attention to the symmetry of the town map or the position of the homes and businesses being positioned where they are. It's not a giant alchemy transmutation circle! You're silly and watch too much anime! It's a Rorschach test. Yeah! And from what I see I see two philosopher sto--stoner podering the meaning of life. Yep! Wo said anything about philosopher stones?! There you go again making stuff up. There's no such thing as homounculus, alchemy, or strange men with scars on their face with an arm transplant. Talk your happy pills and go back to sleep! And if you see a red glow duck and cover!
/Duck and cover doesn't work!
The Rapture is NOT an exit strategy.
Eldavojohn = World Class Karma Whore (TM)
Or, if you want to convert crystals to protein, buy a girl some diamonds and see what she does to thank you...
I know this isn't a new idea. I don't have references handy to prove it isn't, I just know that I have read arguments about it. This theory is used to explain the origins of life (distinct from the theory of evolution). Basically, you have the whole "early earth molecular soup mix with electrical activity providing the spark-o-life" (Miller-Urey Experiment), forming organic compounds, which are then (in some manner) "processed" by crystal structures forming later (?).
It makes me wonder if it wouldn't be possible to study crystals in a similar manner to see whether they could (in some manner) aid the formation of the organic compounds formed by the Miller-Urey (and other similar) experiments into early proteins or protein-like structures? Does anyone know if such a study has already been undertaken? Or, is this idea nothing more than baseless speculation with no foundation in reality? I am sincerely curious...
Reason is the Path to God - Anon
MOD PARENT FUNNY
Dimonds...she'll pretty much have to
Wow, structure, function... everyone has posted good comments. But isn't the real problem understanding how proteins FOLD! We know the make-up of many proteins, but do not understand HOW they work because it is tied up in exactly how they fold. This new method does not address this issue. Scientist are trying to understand how proteins work based on their shape AFTER they have folded. If we could figure out HOW they fold, we wouldn't have to examine each one individually. We could predict the final shape and function based on the knowledge of we have of the protein making intstructions and HOW THEY FOLD. Please people, assume everyone is an idiot before you go debate meaningless crap like how flat the earth is.
7h3$3 4r3n'7 7h3 Ðr01Ð$ ¥0 4r3 £00|{1n9 f0r. M0v3 4£0n9. --OB1
I hope this isn't the first step on the way to creating Ice-Nine!
Crystalization is difficult and, frankly, rather unscientific
You're not kidding. My favorite example is the fact that many crystallographers add diet coke to aid in crystallization.
Thats why I am a member of Team 11108 for FAH!
When I build a machine for a client, I try to encourage them to run the FAH core whenever their computer is on, and install it by default.
How much is your data worth? Back it up now.
"If we could figure out HOW they fold, we wouldn't have to examine each one individually. We could predict the final shape and function based on the knowledge of we have of the protein making intstructions and HOW THEY FOLD." On the right track but knowing the shape a protein will fold to is not enough. We still need to know the structure-function relationship. Knowing how it will fold is a little closer, but it's not the holy grail either. The holy grail is knowing directly from the sequence what the function will be. Then we can make whatever you want. To the best of my limited knowledge knowing the shape a protein will fold into from its sequence is only part way. You still need to know what the function is of that structure you predicted. Unless you have some magical formula that relates structure to function you still need a library of similar structure-function relationships to predict the function of a particular protein and how that might change through further modification. That last part (modification) is the key IMHO.
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.
Well, I guess you have to have your structure already determined. But you just send these guys a PDB and they turn it into a 3D model in glass.
crystalproteins.com
Given that the Sanger institute has over a billion gene sequence on file, and (according to Wikipedia) the Protein Data Bank has about 30-odd thousand structures, and assuming that structure and sequence are of roughly equal scientific interest, can we conclude that determining a protein structure is 30,000 times harder than determining a gene sequence?
How they fold is necessary knowledge to modify a protein. You don't need to know a modified protein's ultimate function BEFORE you make and test it. The testing would tell you that. But the structure IS the function when it comes to proteins, based on how they work. By coupling with complementary receptors, the proteins express themselves many different ways. This is thought to happen with some proteins in the middle of completely folding, thus expressing two separate functions.
7h3$3 4r3n'7 7h3 Ðr01Ð$ ¥0 4r3 £00|{1n9 f0r. M0v3 4£0n9. --OB1
Yup, that's me. Been working toward that for ten years now. No joke.
7h3$3 4r3n'7 7h3 Ðr01Ð$ ¥0 4r3 £00|{1n9 f0r. M0v3 4£0n9. --OB1
i thought if you knew the complete aminoacid sequence of some
dna you would get ROOT access? i mean doesn't the "a""t""g""c"("u") sequence
by threes define the sequence of the amino-acid and thus how
the protein will fold?
I think you are thinking of chromosomes, which owe their structure to proteins.