Wit, grit and a supercomputer yield chemical structure of HIV capsid
May 29, 2013 — 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."
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.
CRCW080520R0JNEA CRCW080520R0FKTA CRCW080520R0FKEB CRCW080520R0FKEAHP CRCW080520R0FKEA CRCW080520K5FKTA CRCW080520K5FKEA CRCW080520K0JNTA CRCW080520K0JNEB CRCW080520K0JNEA CRCW080520K0FKTC CRCW080520K0FKTA CRCW080520K0FKEB CRCW080520K0FKEAHP CRCW080520K0FKEA CRCW0805205RFKTA CRCW0805205RFKEA CRCW0805205KFKTA CRCW0805205KFKEA CRCW0805200RKNEAIF CRCW0805200RJNTA CRCW0805200RJNEB CRCW0805200RJNEA CRCW0805200RFKTA CRCW0805200RFKEB CRCW0805200RFKEA CRCW080522K1FKEB CRCW080522K1FKEA CRCW080522K0JNTA CRCW080522K0JNEB CRCW080522K0JNEAIF CRCW080522K0JNEAHP CRCW080522K0JNEA CRCW080522K0FKTA CRCW080522K0FKEB CRCW080522K0FKEA CRCW0805226RFKTA CRCW0805226RFKEA CRCW0805226KFKTA CRCW0805226KFKEA
http://www.suvsystem.com/a/1925.aspx
