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

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

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."

Welcome to SUV System Ltd!

SUV System Ltd is ISO 90012008 Certified electronics distributor with 10 years of experiences.

We have built up long term business relationship with about many companies which are stockers and authorized agents. we have a steady and reliable supply to meet customer's demands to the greatest extent .Confidently, we are able to lower your cost and support your business with our years of professional service.

SUV System Ltd is Electronic Components Distributor Supplies,Find Quality Electronic Components Supplies Products IC(Integrated Circuits),Connectors,Capacitor,Resistors,Diodes,Transistors,LED at Suvsystem.com. Sourcing Other Energy, Environment, Excess Inventory Products from Manufacturers and Suppliers at Suvsystem.com

Electronic Components distributor:http://www.suvsystem.com

Connectors Distributor:http://www.suvsystem.com/l/Connectors-1.html

IC Distributor:http://www.suvsystem.com/l/IC(Integrated-Circuits)-1.html

LED Distributor:http://www.suvsystem.com/l/LED-1.html

Capacitor Distributor:http://www.suvsystem.com/l/Capacitor-1.html

Transistor Distributor:http://www.suvsystem.com/l/Transistors-1.html

Resistor Distributor:http://www.suvsystem.com/l/Resistors-1.html

Diode Distributor:http://www.suvsystem.com/l/Diodes-1.html

SUV System Ltd insists on the managing faith ofsincereness,speciality,foresight, win-win,so we build up stable-relationship customers located all over the world, including the States, Europe, Argentina, UAE, Malaysia, Australia,and India etc

we are focus on the following fields,and hope we can help you.

CRGV0603F549K CRGV0603F536K CRGV0603F523K CRGV0603F511K CRGV0603F499K CRGV0603F487K CRGV0603F475K CRGV0603F464K CRGV0603F453K CRGV0603F442K CRGV0603F432K CRGV0603F422K CRGV0603F412K CRGV0603F402K CRGV0603F392K CRGV0603F383K CRGV0603J560K CRGV0603J510K CRGV0603J4M7 CRGV0603J4M3 CRGV0603J470K CRGV0603J430K CRGV0603J3M9 CRGV0603J3M6 CRGV0603J3M3 CRGV0603J3M0 CRGV0603J390K CRGV0603J360K CRGV0603J330K CRGV0603J300K CRGV0603J2M7 CRGV0603J2M4 CRGV0603J2M2 CRGV0603J2M0 CRGV0603J270K CRGV0603J240K CRGV0603J220K CRGV0603J200K CRGV0603J1M8 CRGV0603J1M6
http://www.suvsystem.com/a/1748.aspx