High-resolution HIV capsid structure map determines
related atomic models or provides ideas for new drug development
Science and Technology Daily, Beijing, November 22 (intern reporter Zhang Jiaxin) The British Electronic Biological Imaging Center (eBIC) used new technology of electronic tomography and sub-pixel tomographic averaging to determine the capsid protein of HIV and its relationship 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.
The research paper was published in the journal "Science Advances" on the 19th.
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.
In the early stages of HIV-1 replication, the capsid plays a variety of important roles, including protecting the genome from the cell's innate immune response, promoting reverse transcription, and regulating intracellular transport and entry into the nucleus.
Many of these functions are affected by the interaction of the capsid with host cytokines and small molecules.
However, due to the metastable nature 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, which avoids the trauma associated with virion lysis and core separation, but also brings the capsid into contact. To external cytokines and small molecules.
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 dual 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 research, 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.
Editor-in-chief
The capsid protein can be understood as the "invisible cloak" of the virus, which can hide the information of the virus and protect the genetic material inside the virus.
Researchers have conducted long-term studies on the capsid protein of the HIV virus and found that it also plays an important role in the process of viral infection.
Drug companies also use capsid protein as a target for research on AIDS drugs.
Previously, researchers have drawn the structure of the capsid protein, but this time, the researchers used a new method to isolate the intact natural capsid and used the new technology to obtain a higher-resolution image of the composite structure.
More details can help humans find more suitable ways to prevent and fight viruses in terms of transcription and translation.