Navigation Links
Carnegie Mellon scientists find key HIV protein makes cell membranes bend more easily

PITTSBURGH -- Carnegie Mellon University scientists have made an important discovery that aids the understanding of why HIV enters immune cells with ease. The researchers found that after HIV docks onto a host cell, it dramatically lowers the energy required for a cell membrane to bend, making it easier for the virus to infect immune cells. The finding, in press in Biophysical Journal, will provide vital data to conduct future computer simulations of HIV dynamics to help further drug discovery and prevent deadly infections.

“We found that HIV fusion peptide dramatically decreases the amount of energy needed to bend a cell-like membrane,” said Stephanie Tristram-Nagle, associate research professor of biological physics at Carnegie Mellon. “This helps membranes to curve, a necessary step for HIV to fuse with an immune cell as it infects it.”

The Carnegie Mellon scientists used X-rays to study how HIV fusion peptide (part of a larger protein) affected the energy of manufactured lipid bilayers made to mimic normal cell membranes. Lipid bilayers provide a protective barrier for the cell against intruders, yet also contain molecules to recognize and communicate with other cells or get nutrients. Cells also communicate with one another via small, membrane-bound vesicles that contain proteins or other molecular cargo. When delivering their goods, vesicles from one cell fuse with the outermost membrane of another cell to form a series of hybrid structures called fusion intermediates.

Through evolution, viruses have also become skilled at fusing with cells to unload their genetic contents, which turn host cells into virus-producing factories. In the case of HIV, a molecule called gp120 initially helps the virus lock onto its host T cell, a cell critical for maintaining immunity. Another protein — gp41 — then enables HIV to penetrate a T-cell membrane. Fusion takes place specifically through a short stretch of gp41 called fusion peptide 23, or FP-23 for short . Prior studies have shown that FP-23 fuses with, and can even break apart, blood cells and other man-made, cell-like structures called liposomes.

FP-23 likely plays several roles in viral fusion, according to the researchers. One role already suspected is that FP-23 attaches to its T cell victim to facilitate a change in the shape of gp41, which in turn drives uptake of HIV RNA and proteins by the T cell. But the Carnegie Mellon work suggests that FP-23 plays another, equally important function — reducing the free energy of curved fusion intermediates. These fleeting shapes arise and disappear as HIV enters a T cell.

Normally, a cell membrane resists bending. Scientists can quantify the energy needed to overcome this resistance. The Carnegie Mellon team found that FP-23 reduces the energy required to penetrate an artificial cell membrane by up to 13 fold, depending on the thickness of that membrane.

“Reducing this energy should help explain in part how HIV infection occurs so readily,” said Tristram-Nagle. “Our findings definitely will change how theoreticians think about virus-cell interactions. This same phenomenon could provide a general way that viruses use to infect cells, so it will be exciting to look at other viral systems with our experimental method,” she said.

Many different viruses could enter cells by efficiently lowering the energy required to penetrate a cell’s outer membrane, according to Tristram-Nagle and her collaborator, John Nagle, professor of physics and biological sciences at Carnegie Mellon.

The Carnegie Mellon scientists used X-rays to detect the effect of FP-23 on lipid bilayers that mimic cell membranes. Lipid bilayers form different phases that change with temperature, but the “fluid” phase is the most biologically relevant. Using X-ray diffuse scattering, the team quantified structural properties of different lipid bilayers seeded with FP-23 peptides. The lipid bilayers varied in their thicknesses, which affect s the stiffness of cell membranes.

The research was conducted at Cornell University’s CHESS synchrotron, which provides a high-intensity source of X-rays for various studies. In their next trip to this facility, the team plans to study FP-23 together with cholesterol, a molecule known to modulate the stiffness of cell membranes.


'"/>

Source:Carnegie Mellon University


Related biology news :

1. Carnegie Mellon scientists develop tool that uses MRI to visualize gene expression in living animals
2. Robot-based system developed at Carnegie Mellon detects life in Chiles Atacama desert
3. Green catalyst destroys pesticides and munitions toxins, finds Carnegie Mellon University
4. Carnegie Mellon University research reveals how cells process large genes
5. Carnegie Mellon cyLab researchers work to develop new red tide monitoring
6. Team led by Carnegie Mellon University scientist finds first evidence of a living memory trace
7. Carnegie Mellon scientists create PNA molecule with potential to build nanodevices
8. Carnegie Mellon U. transforms DNA microarrays with standard Internet communications tool
9. Carnegie Mellon develops non-invasive technique to detect transplant rejection at cellular level
10. Carnegie Mellon scientists show brain uses optimal code for sound
11. DNA conclusive yet still controversial, Carnegie Mellon professor says
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/15/2016)... 15, 2016 Transparency Market ... Recognition Market by Application Market - Global Industry Analysis Size ... to the report, the  global gesture recognition market ... and is estimated to grow at a CAGR ... 2024.  Increasing application of gesture recognition ...
(Date:6/3/2016)... 2016 Das DOTM ... Nepal hat ein 44 Millionen ... Kennzeichen, einschließlich Personalisierung, Registrierung und IT-Infrastruktur, an ... und Implementierung von Identitätsmanagementlösungen. Zahlreiche renommierte internationale ... teilgenommen, aber Decatur wurde als konformste und ...
(Date:6/1/2016)... , June 1, 2016 Favorable ... Election Administration and Criminal Identification to Boost Global Biometrics ... recently released TechSci Research report, " Global Biometrics Market ... Competition Forecast and Opportunities, 2011 - 2021", the global ... by 2021, on account of growing security concerns across ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... June 23, 2016 /PRNewswire/ - FACIT has announced ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" ... commercialization of a portfolio of first-in-class WDR5 inhibitors ... such as WDR5 represent an exciting class of ... precision medicine for cancer patients. Substantial advances have ...
(Date:6/23/2016)... SANTA MONICA, Calif. , June 23, 2016  The Prostate Cancer ... to pioneer increasingly precise treatments and faster cures for prostate cancer. Members of ... 77 institutions across 15 countries. Read More About the ... ... ...
(Date:6/23/2016)... ... June 23, 2016 , ... STACS DNA Inc., the sample tracking software ... State Crime Laboratory, has joined STACS DNA as a Field Application Specialist. , ... Tremblay, President and COO of STACS DNA. “In further expanding our capacity as a ...
(Date:6/23/2016)... June 23, 2016 ... 2016;12(1):22-8 http://doi.org/10.17925/OHR.2016.12.01.22 Published recently ... peer-reviewed journal from touchONCOLOGY, Andrew D Zelenetz ... of cancer care is placing an increasing burden ... expensive biologic therapies. With the patents on many ...
Breaking Biology Technology: