Navigation Links
Elusive HIV shape change revealed; Key clue to how virus infects cells

Structural biologists at Children's Hospital Boston and Harvard Medical School have shown how a key part of the human immunodeficiency virus (HIV) changes shape, triggering other changes that allow the AIDS virus to enter and infect cells. Their findings, published in the Feb. 24 issue of the journal Nature, offer clues that will help guide vaccine and treatment approaches.

Researchers led by Howard Hughes Medical Institute Investigator Stephen Harrison, PhD, and Bing Chen, PhD, focused on the gp120 protein, part of HIV's outer membrane, or envelope. gp120's job is to recognize and bind to the so-called CD4 receptor on the surface of the cell HIV wants to infect. Once it binds, gp120 undergoes a shape change, which signals a companion protein, gp41, to begin a set of actions that enable HIV's membrane to fuse with the target cell's membrane. This fusion of membranes allows HIV to enter the cell and begin replicating.

The structure of gp120 after it binds to the CD4 receptor and changes its shape was solved several years ago by another group. Harrison and Chen have now described gp120's structure before the shape change, yielding vital before-and-after information on how the molecule rearranges itself when it encounters the CD4 receptor.

"Knowing how gp120 changes shape is a new route to inhibiting HIV ?by using compounds that inhibit the shape change," says Harrison. He notes that some HIV inhibitors already in development seem to inhibit the shape change; the new findings may help pin down how these compounds work and hasten their development into drugs. "The findings also will help us understand why it's so hard to make an HIV vaccine, and will help us start strategizing about new approaches to vaccine development."

The studies, performed in the Children's Hospital Boston Laboratory of Molecular Medicine, used the closely related simian immunodeficiency virus (SIV) as a stand-in for HIV. By aiming an X-ray beam through a crystallized form of gp120, they obtained the first high-resolution three-dimensional images of the protein in its unbound form. They surmounted considerable technical challenges, including difficulty in getting gp120 to form good crystals.

"Without very well-ordered crystals you get a very blurry picture," explains Harrison. "It took a very long time, and lots of computational work, to get that picture to sharpen up enough to get an answer."

One of the lab's first steps will be to determine which shape of gp120 ?bound to the CD4 receptor, or unbound ?is recognized by a person's antibodies. gp120's shape change is an important "escape mechanism" for HIV, allowing the virus to bind to and enter a cell before the immune system can "see" it, notes Harrison.

"We can now compare the bound and unbound forms and try to understand whether there are any immunologic properties that differ and that might provide a route to new vaccine or drug strategies," Harrison says.


'"/>

Source:Children's Hospital Boston


Related biology news :

1. Elusive salamanders have role in developing new sampling models
2. Elusive rust resistance genes located
3. Discovery of key proteins shape could lead to improved bacterial pneumonia vaccine
4. Scientists reveal the shape of a protein that helps retroviruses break into cells
5. Evolution of taste receptor may have shaped human sensitivity to toxic compounds
6. Divergent life history shapes gene expression in brains of salmon
7. Beyond genes: Lipid helps cell wall protein fold into proper shape
8. Mechanism regulating tooth shape formulation found
9. MicroRNAs have shaped the evolution of the majority of mammalian genes
10. The shape of things to come: Morphology database going global
11. Pleasing plant shapes explained by new computer model
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:8/15/2018)... , ... August 15, 2018 , ... Exalto Bearings ... pump and marine industries, has updated its ISO quality management certification to BS EN ... including a strong customer focus and the company’s ability to offer products and services ...
(Date:8/14/2018)... ... 13, 2018 , ... Career fairs provide an ideal setting ... systems at once. However, healthcare professionals often have hectic schedules with little spare ... healthcare providers who wish to explore opportunities and learn about multiple employers from ...
(Date:8/14/2018)... ... August 13, 2018 , ... NRD, LLC – ... P-2021-5602 Cleanroom Ionizing Gun. , The ionizing gun features ergonomic design and ... cartridge, 0.5-micron filter and electropolished OSHA-compliant tip. This can be cleanroom packaged (P-2021-5502) ...
Breaking Biology News(10 mins):
(Date:8/31/2018)... ASTORIA, Ore. (PRWEB) , ... August 29, 2018 ... ... holding Associate Professorships at both the University of Southampton and the Institute of ... and artificial intelligence at sea can dramatically accelerate the exploration and study of ...
(Date:8/29/2018)... ... August 28, 2018 , ... ... of contact lenses, has been ranked in 1138th place on the 27th annual ... , The list represents the most successful companies within the American economy’s ...
(Date:8/26/2018)... LINDA, Calif. (PRWEB) , ... August 23, 2018 ... ... virtual events for tech innovators, engineers, and scientists from around the world, will ... Immunology 2018 will cover an array of industries and disciplines, encompassing various research ...
(Date:8/21/2018)... ... August 21, 2018 , ... ... medical device compliance and commercialization, has just released a new paper discussing ... presented by Dr. Mario Kossmann, ESEP at the 28th Annual INCOSE International ...
Breaking Biology Technology: