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Scientists Unveil Structure of Adenovirus

timothy posted more than 3 years ago | from the after-the-unveiling-is-the-fun-part dept.

Medicine 20

An anonymous reader contributes this snippet from Medical News Daily, which begins a story of some interesting medical detective work: "After more than a decade of research, Scripps Research Institute scientists have pieced together the structure of a human adenovirus—the largest complex ever determined at atomic resolution. The new findings about the virus, which causes respiratory, eye, and gastrointestinal infections, may lead to more effective gene therapy and to new anti-viral drugs."

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Would have got first post... (-1, Offtopic)

Anonymous Coward | more than 3 years ago | (#33403908)

...but I caught a virus ;-;

Re:Would have got first post... (-1, Troll)

Anonymous Coward | more than 3 years ago | (#33403930)

Homosexuality isn't a virus, stop trying to explain your faggot behavior by saying that you're not in control of your repulsive sexual desire.

Re:Would have got first post... (0)

Anonymous Coward | more than 3 years ago | (#33404160)

You know, if I was a homosexual, you'd be the last person I was aroused by. Similarly, when a stunning blonde female makes racist remarks, I can no longer stand the very sight of her. So why is it that you feel threatened?

Re:Would have got first post... (0)

Anonymous Coward | more than 3 years ago | (#33404328)

eh, i fuck her all the same, but that's just me.

This seems related. No paywall (5, Informative)

wierd_w (1375923) | more than 3 years ago | (#33403938)

Found some tasty information for those who are inclined to produce their own 3D model of a human adenovirus. Gives some juicy details that the linked article doesn't. A quasi-atomic model of human adenovirus type 5 capsid [nih.gov]

Re:This seems related. No paywall (1)

Provocateur (133110) | more than 3 years ago | (#33403978)

adeno, man, with my clunker of a PC should I go and check out what you linked to even?

Re:This seems related. No paywall (0, Offtopic)

countertrolling (1585477) | more than 3 years ago | (#33404676)

Very good stuff, but for some, it's kind of like expecting a web page designer or java programmer to understand machine code. Our dot gov sites are definitely some of the best stuff on the net for anybody looking for an education. For that I'm grateful... tax money very well spent

Singularity is near (1)

sznupi (719324) | more than 3 years ago | (#33403940)

Well, at the least we can give immortality (assuming you count those as alife in the first place) to our pathogens...

On the second thought, we're quite good at providing this for a long time.

Heroic.. and ongoing (2, Insightful)

mattr (78516) | more than 3 years ago | (#33404148)

The TFA is quite interesting and seems to have been a real heroic quest. They haven't completed it to the last little bit, as it is highly resistant in places. Quite a mammoth!

Re:Heroic.. and ongoing (1)

slick7 (1703596) | more than 3 years ago | (#33404982)

The TFA is quite interesting and seems to have been a real heroic quest. They haven't completed it to the last little bit, as it is highly resistant in places. Quite a mammoth!

Wait til they weaponize it. Where's your technology now?

TFA Omits a Second Study (5, Informative)

structural_biologist (1122693) | more than 3 years ago | (#33404784)

The Aug 27 issue of Science, in which the x-ray crystallography study from Scripps appears, actually pubished two papers that describe the structure of adenovirus. The two papers use different techniques to achieve the same ends: the study from the researchers at Scripps grew crystals of the virus and studdied the x-ray diffraction patterns to deduce the structure of the virus. The other paper, done in collaboration between researches at UCLA and Xiangtan University in China, used a technique called cryo-electron microscopy. In this technique, the researchers freeze samples of the virus and use an electron microscope to take tens of thousands of pictures of different viruses within their samples. Although the pictures only give 2D projections of the virus structure, the individual electron microscopy images show the virus from different perspectives. By computationally aligning the images, they can reconstruct the 3 dimensional structure of the virus from the many 2D images taken. While this technique avoids the inherent difficulties of producing crystals (a process that can take decades for some samples), until very recently it has been difficult to achieve high resolution structures using this method. The cryo-EM adenovirus structure is one of only a handful of atomic resolution cryo-EM structures that have been solved to date.

While both studies are very informative and represent scientific tours de force for their respective techniques, it is interesting that the Medical Daily focuses only on the x-ray crystallography study from Scripps. Indeed, in a commentary published by Science that accompanies the articles, Prof. Stephen Harrison of Harvard Medical School (the first person to describe the full structure of a virus) writes that, "Indeed, the cryo-EM density map of Liu et al. appears to be substantially clearer and more interpretable than the x-ray density map of Reddy et al." Perhaps Medical Daily needs to do a better job of doing their homework.

The cryo-EM study is available at the following link (subscription required): http://www.sciencemag.org/cgi/content/abstract/329/5995/1038 [sciencemag.org]

Re:TFA Omits a Second Study (3, Interesting)

the gnat (153162) | more than 3 years ago | (#33405072)

While this technique avoids the inherent difficulties of producing crystals (a process that can take decades for some samples), until very recently it has been difficult to achieve high resolution structures using this method. The cryo-EM adenovirus structure is one of only a handful of atomic resolution cryo-EM structures that have been solved to date.

A large part of the reason why this is possible is the high internal symmetry of viral particles; I think all of the atomic-resolution cryo-EM structures so far have also been of highly symmetric structures like bacterial chaperonins, or other viruses. (The same symmetry also makes crystallography easier, for different reasons.) The only other EM structure that I'm aware of at better than 4 Angstrom resolution is also of a virus, published a few months ago by the same group at UCLA. For highly asymmetric structures such as ribosomes, crystallography is still far ahead of EM as far as resolution is concerned - although the bottleneck of crystallization remains a major problem.

it is interesting that the Medical Daily focuses only on the x-ray crystallography study from Scripps. . . Perhaps Medical Daily needs to do a better job of doing their homework.

If you scroll to the end of the story, you'll see "Provided by Scripps Research Institute" in tiny gray letters. It's just a press release from Scripps, in other words - standard operating procedure for research institutions when someone scores a high-profile article.

Re:TFA Omits a Second Study (1)

oldhack (1037484) | more than 3 years ago | (#33405330)

Poking around Medical Daily, it seems to be a straight-up PR operation. It's been spamming slashdot with some frequency.

cryoEM vs crystallography and structural virology (0)

Anonymous Coward | more than 3 years ago | (#33407270)

For the general public, the most important distinction about cryoEM and xray crystallography involves the consequences of preparing the samples for study.

X-ray crystallography usually requires carefully prepared and concentrated proteins. By treating them with chemicals not normally found in their natural environment, it is possible to induce atypical behavior and structures. In fact, crystallography literally demands that the proteins become static, which is not their normal behavior. In comparison, cryo-EM literally freezes a protein sample instantly from whatever conformation it was in. Maybe it won't be possible to get good data out of it, but the structure you have frozen will probably be a more relevant one, closer to what it truly would be in nature.

Historically, cryoEM was used in conjunction with crystallography: cryoEM would be used to get a low-resolution big-picture structure, and the details would be filled in with high-resolution structures obtained of the individual smaller subunits that make up the whole capsid.

Each approach is very useful, but as a consequence of how the structures are obtained, the data collected can mean very different things. My personal belief is that the motion of the capsids (described somewhat in the linked article) is very important, but I am also biased since that is my area of study.

If you want to have a look at more of Vijay Reddy's work, have a look here: http://viperdb.scripps.edu/.

Re:cryoEM vs crystallography and structural virolo (1)

structural_biologist (1122693) | more than 3 years ago | (#33416770)

X-ray crystallography usually requires carefully prepared and concentrated proteins. By treating them with chemicals not normally found in their natural environment, it is possible to induce atypical behavior and structures. In fact, crystallography literally demands that the proteins become static, which is not their normal behavior. In comparison, cryo-EM literally freezes a protein sample instantly from whatever conformation it was in. Maybe it won't be possible to get good data out of it, but the structure you have frozen will probably be a more relevant one, closer to what it truly would be in nature.

These are all good points, especially the point that cryo-EM helps avoid artifacts induced by crystal packing. However, I'm not sure cryo-EM helps with the issue of conformational flexibility of these large complexes. Even though the cryo-EM samples will freeze the sample in whatever conformation it was in, the single particle reconstruction methods used to analyze the EM data will average over the conformational heterogeneity, so you would end up losing most of that information in your final structure anyway. The same averaging over conformational heterogeneity occurs in crystallography except in the data acquisition step instead of the data analysis step. While it is in principle possible to sort out the different conformers in your sample during image classification, this is very difficult to do (because the cryo-EM images have such poor resolution and low contrast) and would likely only catch very large structural rearrangements.

Re:cryoEM vs crystallography and structural virolo (1)

anguirus.x (1463871) | more than 3 years ago | (#33421860)

Proteins are not static in crystals formed for crystallography. They are highly dynamic structures, and in the case of proteins many maintain their activity even while crystallized, meaning they have full or nearly full functional mobility. This is one of the great advantages to x-ray crystallography. The object being imaged is not static. There is information about the mobility of atoms, and sometimes even ion occupancies can be deduced from the data. So while it is possible to induce atypical behavior and structures, you take steps to ensure that the protein in the crystal behaves as protein in the cell. Practically, however, it's not an issue.

Possible AIDS (1)

Murdoch5 (1563847) | more than 3 years ago | (#33405504)

New antiviral, Nice maybe this can start a new aids solution or at least bring us closer to a point where we can start on new solutions.

Re:Possible AIDS (1)

BioSlayer (1620455) | more than 3 years ago | (#33407714)

New antiviral, Nice maybe this can start a new aids solution or at least bring us closer to a point where we can start on new solutions.

Adenoviruses themselves were used in genetic engineering/treatment as carrier molecules to genetic material that aims at replacing a faulty one in the cell for example. These viruses DNAs are inherently double stranded and they don't incorporate themselves in the cell DNA, hence, upon cell duplication the viruses are lost. While this is an obstacle in introducing persisting genetic therapy and that re-administration of the correct DNA-laden virus is warranted this could also explain why infections caused by adenoviruses does wade - off (I stand to be corrected)...

On the other hand HIV is a small retrovirus (adenoviruses have upto 1 million amino-acids ), that means that its genetic matter is a short RNA, it has to use the cell it infects DNA manufacturing machinery for it to make copies of itself, this is done by back-translating RNA into DNA that gets incorporated into the nucleus and then proceeding forward using the cell promoters to bring about these copies. HIV is more tricky to handle than many other viruses.

Another thing to look into is the possibility of using siRNA and microRNA as adjuncts to genetic treatment that involves adenviruses, that can potentially carry with it the effect of prolonging the treatment efficacy....

little known problem with respiratory viruses (1)

Goraek (398392) | more than 3 years ago | (#33406778)

Viruses such as adenovirus and rhinovirus affect mucous membranes.
The urinary tract has mucous membranes. Adenovirus urethritis in men is ~exquisitely~ painful.

Moral of the story: your wang getting a 'head cold' isn't fun, if she has the sniffles then she should watch her oral intake.

-IAAD

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