Conformational transitions of the HIV-1 Gag polyprotein upon multimerization and gRNA binding

Banerjee, Puja; Voth, Gregory A.

doi:10.1016/j.bpj.2023.11.017

Cited by 4 publications

(2 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cholesterol helps counteract unfavorable packing of saturated and unsaturated lipids in membranes in general and maintains structural integrity and membrane fluidity. Experimental studies on HIV-1 assembly dynamics have suggested that Gag multimerization on the PM induces clustering of specific lipid species like PIP2 and cholesterol in the inner leaflet, which in turn remodels the outer leaflet through trans-bilayer coupling. ,− The relationship between MA multimerization and membrane binding is still unclear along with its impact on the lateral organization of lipids in each PM leaflet. , …”

Section: Introductionmentioning

confidence: 99%

Cooperative Membrane Binding of HIV-1 Matrix Proteins

Banerjee,

Monje-Galvan,

Voth

2024

J. Phys. Chem. B

Self Cite

View full text Add to dashboard Cite

The HIV-1 assembly process begins with a newly synthesized Gag polyprotein being targeted to the inner leaflet of the plasma membrane of the infected cells to form immature viral particles. Gag−membrane interactions are mediated through the myristoylated (Myr) N-terminal matrix (MA) domain of Gag, which eventually multimerize on the membrane to form trimers and higher order oligomers. The study of the structure and dynamics of peripheral membrane proteins like MA has been challenging for both experimental and computational studies due to the complex transient dynamics of protein−membrane interactions. Although the roles of anionic phospholipids (PIP2, PS) and the Myr group in the membrane targeting and stable membrane binding of MA are now well-established, the cooperative interactions between the MA monomers and MA-membrane remain elusive in the context of viral assembly and release. Our present study focuses on the membrane binding dynamics of a higher order oligomeric structure of MA protein (a dimer of trimers), which has not been explored before. Employing time-lagged independent component analysis (tICA) to our microsecond-long trajectories, we investigate conformational changes of the matrix protein induced by membrane binding. Interestingly, the Myr switch of an MA monomer correlates with the conformational switch of adjacent monomers in the same trimer. Together, our findings suggest complex protein dynamics during the formation of the immature HIV-1 lattice; while MA trimerization facilitates Myr insertion, MA trimer−trimer interactions in the immature lattice can hinder the same.

show abstract

Section: Introductionmentioning

confidence: 99%

Cooperative Membrane Binding of HIV-1 Matrix Proteins

Banerjee,

Monje-Galvan,

Voth

2024

J. Phys. Chem. B

Self Cite

View full text Add to dashboard Cite

show abstract

“…As such, mathematical and biophysical models can be helpful in augmenting these experimental investigations. To date, the vast majority of computational models of self-assembly have focused on the assembly of viral capsids at various levels of biophysical resolution ( 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ). While some work has been done using molecular dynamics to study the assembly of molecular machines such as the ribosome ( 46 , 47 , 48 , 49 , 50 ), there has been comparatively little work investigating the assembly of rings and stacked rings such as the proteasome.…”

Section: Introductionmentioning

confidence: 99%

Modeling reveals the strength of weak interactions in stacked-ring assembly

Lagunes,

Briggs,

Martin-Holder

et al. 2024

Biophysical Journal

View full text Add to dashboard Cite

HIV-1 assembly – when virology meets biophysics

Lacouture,

Carrio,

Favard

et al. 2024

Journal of Cell Science

View full text Add to dashboard Cite

Cells naturally produce vesicles that bud from different lipid membranes using dedicated molecular machineries. Enveloped RNA viruses, including human immunodeficiency virus type 1 (HIV-1), also generate particles that bud from host cell membranes by hijacking cellular factors and signaling pathways similar to those involved in the budding of extracellular vesicles. HIV-1 buds from the host cell plasma membrane mainly via the self-assembly of Gag, a structural protein. Gag is a polyprotein that forms assembly complexes containing viral genomic RNA (gRNA), host cell lipids and proteins. HIV-1 Gag binds and segregates host cell plasma membrane lipids while self-assembling simultaneously on the gRNA and the plasma membrane. This self-assembly causes membrane bending and formation of a new viral particle with the help of host cell proteins, likely including cortical actin-associated factors. However, it is unclear whether the energy of Gag self-assembly is sufficient to generate new HIV-1 particles. In this Review, we discuss these processes in the light of the past and recent virology literature, incorporating lessons from studies on the quantitative biophysics of viral self-assembly, and explore how Gag might reorganize the plasma membrane and divert host cell membrane curving proteins and cortical actin-related factors to achieve particle assembly and budding.

show abstract

Conformational transitions of the HIV-1 Gag polyprotein upon multimerization and gRNA binding

Cited by 4 publications

References 92 publications

Cooperative Membrane Binding of HIV-1 Matrix Proteins

Cooperative Membrane Binding of HIV-1 Matrix Proteins

Modeling reveals the strength of weak interactions in stacked-ring assembly

HIV-1 assembly – when virology meets biophysics

Contact Info

Product

Resources

About