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NEW YORK DAWN™ > Blog > Health > Scientists uncover the perform of a mysterious HIV part
Scientists uncover the perform of a mysterious HIV part
Health

Scientists uncover the perform of a mysterious HIV part

Last updated: February 28, 2025 4:57 am
Editorial Board Published February 28, 2025
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To change into infectious, HIV should endure a maturation course of. In immature HIV, matrix proteins (crimson) type a unfastened lattice (high proper), whereas in mature HIV, the formation of a secure lattice is triggered by the protein SP2 (blue, backside proper). Credit score: Margot Riggi, MPI of Biochemistry

Researchers from the Max Planck Institute of Biochemistry have found the mechanism behind an essential step within the life cycle of HIV. Working along with groups at Heidelberg and Yale Universities, they discovered that the enigmatic “spacer peptide 2,” one of many virus parts, performs a key function in changing immature HIV-1 particles into infectious particles. The outcomes of the research have been printed within the journal Nature.

HIV-1 particles are launched from contaminated cells in an immature, non-infectious type. The primary constructing materials for a virus particle is about 2,000 copies of a protracted, rod-shaped protein known as Gag. To change into infectious, HIV has to endure a maturation course of. This includes the HIV-1 protease (a viral enzyme), that cuts up Gag into six smaller proteins together with the capsid protein and the matrix protein. This causes an enormous structural rearrangement of the virus parts.

For a few years, scientists have explored the structural modifications of the virus capsid which encases the genome. In distinction, a lot much less is thought in regards to the virus matrix—the outer protein shell immediately beneath the lipid membrane that envelops the virus. Researchers led by John Briggs, director and structural biologist on the Max Planck Institute of Biochemistry, have now labored out how the matrix protein rearranges throughout maturation into the infectious particle.

They used the newest cryo-electron microscopes to picture virus particles, after which used computational picture evaluation to derive very detailed 3D fashions of the viral proteins. Unexpectedly, they discovered that the rearrangement of the matrix is triggered by “spacer peptide 2,” which sticks to the matrix and causes it to pack collectively differently.

Spacer peptide 2 is one other one of many six parts fashioned by reducing up Gag, however its perform was unknown till now. Binding of spacer peptide 2 to matrix protein permits the virus to fuse with goal cells extra rapidly.

Briggs explains, “In our lab, we obtained the first structural data about the matrix in 2021, but we didn’t know what caused it to rearrange when the virus matures. In this new study we produced much more detailed 3D views of the matrix layer, which was key to understanding what is going on.”

James Stacey and Dominik Hrebík, the 2 first authors of the research, clarify their findings. Stacey says, “The virus matrix has a pocket in its mature form. We knew that something binds there, but we thought it was a lipid from the membrane. Now we can see that it is spacer peptide 2. We wonder whether this pocket could be a target for drug molecules in the future.”

Hrebík says, “Until now, the function of spacer peptide 2 was not known. Thanks to high-resolution cryo-electron microscopy, we have seen that this peptide, after its release, binds directly to the matrix proteins and links the proteins together in the mature virus.”

Briggs concludes, “HIV-1 is probably the most studied virus, but there are still important steps in its replication we don’t yet understand.”

Extra info:
James C. V. Stacey et al, The conserved HIV-1 spacer peptide 2 triggers matrix lattice maturation, Nature (2025). DOI: 10.1038/s41586-025-08624-9

Offered by
Max Planck Society

Quotation:
Scientists uncover the perform of a mysterious HIV part (2025, February 27)
retrieved 27 February 2025
from https://medicalxpress.com/information/2025-02-scientists-function-mysterious-hiv-component.html

This doc is topic to copyright. Aside from any honest dealing for the aim of personal research or analysis, no
half could also be reproduced with out the written permission. The content material is offered for info functions solely.

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