High resolution HIV capsid structure map determination

High resolution HIV capsid structure map determination

About the atomic model or provide ideas for new drug development

HIV capsids FIG high resolution high-resolution determination of HIV capsids FIG determinationof atomic model or provide drug development ideas relating to the atomic model of drug development or to provide ideas about the atomic model or provide drug development ideas

Science and Technology Daily Beijing November 22 (by intern reporter Zhang Jiaxin) UK electronics Biological Imaging Center (eBIC) using electron tomography and the average of the new technology sub-pixel fault map, to determine the AIDS virus (HIV) capsid protein, and with The composite structure image of the host cell factor interaction with a resolution of about 5.
4 angstroms
.

Researchers have also established an atomic model of the entire HIV capsid protein, or provide new ideas for the development of anti-HIV drugs targeting the capsid protein

AIDS

The lead author of this breakthrough paper, Dr.
Tao Ni (transliteration) from Oxford University, explained that HIV is a retrovirus whose RNA genome is encapsulated in a conical capsid
.

During the infection process, HIV assembles and buds with immature virions of Gag polyprotein, undergoes proteolysis and conformational changes, and transforms from immature spherical to mature conical capsids

However, due to the metastable properties of HIV-1 capsids, it has been challenging to isolate the quantity and concentration of intact natural capsids suitable for high-resolution structural analysis
.

In order to solve this problem, the research team devised a new method of adding a pore-forming toxin to the membrane of HIV virus-like particles.

After establishing the experimental method, the researchers studied the interaction between the real HIV capsid and the cytokine cyclophilin A (CypA) and the small molecule cofactor inositol hexaphosphate (IP6)
.

Then, the research team performed electronic tomography and sub-tomography averaging on these samples

Using this new technology, the team separately revealed the structure of the HIV capsid and the structure of its complex with CypA and IP6
.

These structures confirmed the double IP6 binding sites in the mature HIV capsid, and provided a new idea for the role of IP6 and CypA in regulating the stability of the HIV capsid

Zhang Peijun, director of eBIC and professor of structural biology at the University of Oxford who led the study, concluded that they used the information obtained from electronic tomography to establish an atomic model of the entire HIV capsid, which can be used as a "blueprint for the development of capsid-targeted anti-AIDS drugs.
" "
.

The perforation of the enveloped virus membrane also provides a new method for studying the host-virus interaction of other virus systems