Featured Research

from universities, journals, and other organizations

Wit, grit and a supercomputer yield chemical structure of HIV capsid

Date:
May 29, 2013
Source:
University of Illinois at Urbana-Champaign
Summary:
Researchers report that they have determined the precise chemical structure of the HIV capsid, a protein shell that protects the virus's genetic material and is a key to its virulence. The capsid has become an attractive target for the development of new antiretroviral drugs.

The researchers used the supercomputer Blue Waters to determine the complete HIV capsid structure, a simulation that accounted for the interactions of 64 million atoms.
Credit: Klaus Schulten/Juan Perilla

A team led by researchers at the University of Pittsburgh School of Medicine has described for the first time the 4-million-atom structure of the HIV's capsid, or protein shell. The findings, highlighted on the cover of the May 30 issue of Nature, could lead to new ways of fending off an often-changing virus that has been very hard to conquer.

Scientists have long struggled to decipher how the HIV capsid shell is chemically put together, said senior author Peijun Zhang, Ph.D., associate professor, Department of Structural Biology, University of Pittsburgh School of Medicine.

"The capsid is critically important for HIV replication, so knowing its structure in detail could lead us to new drugs that can treat or prevent the infection," she said. "This approach has the potential to be a powerful alternative to our current HIV therapies, which work by targeting certain enzymes, but drug resistance is an enormous challenge due to the virus' high mutation rate."

Previous research has shown that the cone-shaped shell is composed of identical capsid proteins linked together in a complex lattice of about 200 hexamers and 12 pentamers, Dr. Zhang said. But the shell is non-uniform and asymmetrical; uncertainty remained about the exact number of proteins involved and how the hexagons of six protein subunits and pentagons of five subunits are joined. Standard structural biology methods to decipher the molecular architecture were insufficient because they rely on averaged data, collected on samples of pieces of the highly variable capsid to identify how these pieces tend to go together.

Instead, the team used a hybrid approach, taking data from cryo-electron microscopy at an 8-angstrom resolution (a hydrogen atom measures 0.25 angstrom) to uncover how the hexamers are connected, and cryo-electron tomography of native HIV-1 cores, isolated from virions, to join the pieces of the puzzle. Collaborators at the University of Illinois then used their new Blue Waters supercomputer to run simulations at the petascale, involving 1 quadrillion operations per second, that positioned 1,300 proteins into a whole that reflected the capsid's known physical and structural characteristics.

The process revealed a three-helix bundle with critical molecular interactions at the seams of the capsid, areas that are necessary for the shell's assembly and stability, which represent vulnerabilities in the protective coat of the viral genome.

"The capsid is very sensitive to mutation, so if we can disrupt those interfaces, we could interfere with capsid function," Dr. Zhang said. "The capsid has to remain intact to protect the HIV genome and get it into the human cell, but once inside it has to come apart to release its content so that the virus can replicate. Developing drugs that cause capsid dysfunction by preventing its assembly or disassembly might stop the virus from reproducing."

The project was funded by National Institutes of Health grants GM082251, GM085043 and GM104601 and the National Science Foundation.

"By using a combination of experimental and computational approaches, this team of investigators has produced a clearer picture of the structure of HIV's protective covering," said the National Institutes of Health's Michael Sakalian, Ph.D., who oversees this and other grants funded through an AIDS-related structural biology program. "The new structural details may reveal vulnerabilities that could be exploited by future therapeutics."


Story Source:

The above story is based on materials provided by University of Illinois at Urbana-Champaign. Note: Materials may be edited for content and length.


Journal Reference:

  1. Gongpu Zhao, Juan R. Perilla, Ernest L. Yufenyuy, Xin Meng, Bo Chen, Jiying Ning, Jinwoo Ahn, Angela M. Gronenborn, Klaus Schulten, Christopher Aiken, Peijun Zhang. Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Nature, 2013; 497 (7451): 643 DOI: 10.1038/nature12162

Cite This Page:

University of Illinois at Urbana-Champaign. "Wit, grit and a supercomputer yield chemical structure of HIV capsid." ScienceDaily. ScienceDaily, 29 May 2013. <www.sciencedaily.com/releases/2013/05/130529133403.htm>.
University of Illinois at Urbana-Champaign. (2013, May 29). Wit, grit and a supercomputer yield chemical structure of HIV capsid. ScienceDaily. Retrieved August 27, 2014 from www.sciencedaily.com/releases/2013/05/130529133403.htm
University of Illinois at Urbana-Champaign. "Wit, grit and a supercomputer yield chemical structure of HIV capsid." ScienceDaily. www.sciencedaily.com/releases/2013/05/130529133403.htm (accessed August 27, 2014).

Share This




More Health & Medicine News

Wednesday, August 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Predicting Heart Transplant Rejection With a Blood Test

Predicting Heart Transplant Rejection With a Blood Test

Ivanhoe (Aug. 27, 2014) Now a new approach to rejection of donor organs could change the way doctors predict transplant rejection…without expensive, invasive procedures. Video provided by Ivanhoe
Powered by NewsLook.com
Better Braces That Vibrate

Better Braces That Vibrate

Ivanhoe (Aug. 27, 2014) The length of time you have to keep your braces on could be cut in half thanks to a new device that speeds up the process. Video provided by Ivanhoe
Powered by NewsLook.com
Smartphone App Tracks Your Heart Rate

Smartphone App Tracks Your Heart Rate

Ivanhoe (Aug. 27, 2014) A new app that can track your heart rate 24/7 is available for download in your app store and its convenience could save your life. Video provided by Ivanhoe
Powered by NewsLook.com
Stroke in Young Adults

Stroke in Young Adults

Ivanhoe (Aug. 27, 2014) A stroke can happen at any time and affect anyone regardless of age. This mother chose to give her son independence and continue to live a normal life after he had a stroke at 18 years old. Video provided by Ivanhoe
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

More Coverage


Computer Simulations Help Scientists Understand HIV-1 Infection

May 30, 2013 Scientists have long been unable to fully explain how infections attack the body, but now a team of researchers has taken a step closer to understanding how the process works in HIV-1. The results ... read more
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins