Mappata tutta la struttura del Capside

Da Gex Mer 19 Gen - 22:17

Mappata tutta la struttura del Capside dell'Hiv.
Il capside e' la struttura proteica che circonda il materiale genetico dell'Hiv.
Il capside del'hiv e' molto flessibile in grado di cambiare la sua forma, e questo uno dei grandi problemi per cui l'organismo non riesce a bloccare il virus.
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Scientists Map Key Structure HIV Uses to Infect Cells
Details on gene-delivering 'capsid' could point the way to new drugs

Posted: January 19, 2011

WEDNESDAY, Jan. 19 (HealthDay News) -- U.S. scientists say they've finished the first detailed description of the complete protein package within the human immunodeficiency virus (HIV) thought to be essential to its ability to infect human cells.

HIV uses this protein package, a cone-shaped container called a "capsid," to transport its genetic material into the host cell, after binding with receptors on the cell's surface.

After gaining entry, the capsid releases its genetic cargo into the cell, helping HIV to hijack the cell's machinery to replicate its own genes and proteins, according to a news release from The Scripps Research Institute in La Jolla, Calif.

As new viruses form, the genetic material is incorporated into round, immature capsids that HIV uses to flee from the cell. Each round capsid then reconfigures itself into its characteristic cone shape so it can help the virus move on and infect other cells in a similar fashion.

However, if any part of this capsid rearrangement were to be blocked, it would render HIV no longer infectious, the scientists said. And that could point the way to new drugs aimed at fighting HIV/AIDS.

Much more work will need to be done before that kind of research can begin, stressed senior study author Dr. Mark Yeager, a Scripps Research professor and staff cardiologist and chair of the Molecular Physiology and Biological Physics Department at The University of Virginia School of Medicine.

"We don't have the full story yet, but we have volume one," Yeager said in the Scripps news release.

The findings appear in the Jan. 19 issue of the journal Nature.

Yeager's team noted that the capsid structure of HIV differs greatly from that of many other viruses. For example, the capsid of the poliovirus has a rigid, symmetrical structure, while the HIV capsid is more flexible and can take on slightly varied shapes. Yeager, along with Owen Pornillos and Barbie Ganser-Pornillos, a husband-and-wife team working in his lab, spent years figuring out the precise atomic structure behind capsid formation.

They now plan to use computer programs to hunt for weak spots in the capsid's structure that might offer promising targets for drug development.

More information

Find out more about HIV/AIDS at the U.S. Centers for Disease Control and Prevention.

Da Gex Mer 19 Gen - 22:31

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Da Gex Mer 19 Gen - 22:34

Scripps Research Details HIV Capsid Structure, Potential Drug
By: Bradley Fikes — January 19th, 2011

HIV is the subject of a duo of papers this week from Scripps Research Institute scientists.
The first concerns newly created compounds that inhibit HIV replication and fight inflammation. It was published in in the Proceedings of the National Academy of Sciences.
The second is a technical feat: an atomic-scale modelling of the HIV capsid, the cone-shaped protein container the virus injects into human cells. The capsid contains the genetic instructions for hijacking the infected cell to make more HIV particles. It was published in Nature. (Abstract: Subscription or payment required to read full text).

The capsid of HIV is a conical fullerene shell that comprises about 250 hexamers (orange) and exactly 12 pentamers (gold) of the viral CA protein. In the new study, the researchers determined X-ray crystal structures of these building blocks, which enabled modeling of the complete capsid at atomic resolution. The continuously varying lattice curvature in the fullerene cone can be explained simply by two rigid body rotations around two assembly interfaces of CA. (Graphics by Owen Pornillos, Barbie Ganser-Pornillos, Kelly Dryden, and Mark Yeager.)

The first paper results from a study of the plant Hypericum chinense, known in Japan as biyouyanagi. The flower-bearing plant makes chemicals known as biyouyanagins known to have anti-HIV and anti-tumor properties. The plant is from the same family that produces St. John’s wort.
Those properties piqued the curiosity of TSRI chemistry wizard K.C. Nicolaou, according to a Scripps press release. Nicolaou is chair of the department of chemistry, Aline W. and L.S. Skaggs Professor of Chemical Biology, and Darlene Shiley Chair in chemistry. His lab is known for a number of accomplishments over the years, such as the total synthesis of the cancer drug Taxol.

K. C. Nicolaou

The newly discovered biyouyanagins are small molecules, which are more easily administered orally than large molecules, such as proteins, which usually have to be injected.
The scientists plan to tweak one especially promising chemical into a drug candidate. If it passes lab and animal studies, the drug will be tested in humans.
The second paper “Atomic Level Modeling of the HIV Capsid”, was prepared by a research team from TSRI and the University of Virginia. The study’s senior is author Mark Yeager, a TSRI professor and staff cardiologist and chair of the Molecular Physiology and Biological Physics Department at The University of Virginia School of Medicine.
According to the TSRI press release:
“The work is the culmination of studies carried out over the last decade looking at different portions of the cone-shaped container, or the capsid. The final piece of the puzzle, described in an article published in Nature on January 20, 2011, details the structure of the two ends of the cone ….
Having solved the atomic structures of both CA hexamers and pentamers, Yeager and colleagues for the first time were able to build a complete atomic model of the mature HIV capsid.
The researchers now plan to further refine the model using sophisticated computer programs to determine the stability of the structure in different regions and to identify possible “weak” points they can target using newly designed drugs.
They will also begin studying the structure of the immature capsid to determine how this version of the capsid transitions to the mature form—a step in the virus lifecycle that has remained mysterious.
“We don’t have the full story yet, but we have volume one,” says Yeager.”
The paper was funded by the U.S. National Institutes of Health and by P50 funding from the Center for the Structural Biology of Host Elements in Egress, Trafficking, and Assembly of HIV (CHEETAH), which is based at the University of Utah.

Tags: Chemistry, HIV

This entry was posted on Wednesday, January 19th, 2011 at 11:18 am and is filed under Brad’s Sci-Tech Blog, Minding Your Business. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.

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