gag

What is GAG protein?

GAG gene (R-spondin 3) is a protein coding gene which encodes a protein called Gag protein. This protein is a multifunctional polyprotein that plays a critical role in the assembly, release, and maturation of the HIV-1 virus particle. It consists of several domains including matrix (MA), capsid (CA), nucleocapsid (NC), and p6, which facilitate various stages of the viral life cycle, from packaging the viral genome to forming the viral core structure. Gag also interacts with numerous host cell proteins, implicating it in the manipulation of the host cellular environment to support viral replication. The GAG protein is consisted of 530 amino acids and GAG molecular weight is approximately 58.3 kDa.

What is the function of GAG protein?

HIV Gag protein is a multifunctional polyprotein that orchestrates several steps in the viral life cycle, including packaging of the viral genome, assembly and budding of virus particles, and early post-entry events. It consists of different domains like matrix (MA), capsid (CA), nucleocapsid (NC), and p6, each playing specific roles. For instance, MA targets Gag to the plasma membrane, CA forms the structural core of the virus, NC binds to viral RNA, and p6 facilitates virus release. Additionally, Gag interacts with numerous host cell proteins to modulate the environment for viral replication.

Fig1. HIV-1 budding process facilitated by Gag p6 and viral replication promoted by Vpr. (Xiaowei Chen, 2024)

GAG related signaling pathway

The HIV Gag protein plays a central role in the early stages of the HIV life cycle, particularly in the assembly, release, and maturation of the virus particle. It accomplishes this by interacting with various host cell proteins and the viral genome. Moreover, Gag protein engagement with cellular machinery is crucial for processes such as the activation of the L-type calcium channel (CaV1.2), which can modulate disease progression in Marfan syndrome, a condition related to FBN1 rather than Gag. However, in the context of HIV, Gag interacts with factors like TSG101 and the ESCRT pathway, which are key to viral budding and release. The protein also plays a role in the post-entry phase of the viral life cycle, including uncoating and reverse transcription, which are essential steps for the initiation of a new infection cycle.

GAG related diseases

HIV Gag protein is central to the development of HIV-1, as it is the primary structural protein driving the assembly and release of new virus particles. Mutations in the Gag protein can significantly impact the infectivity and replication of HIV, contributing to the progression of HIV-1 disease. Furthermore, Gag is involved in the early stages of viral infection, including viral entry into host cells and the subsequent reverse transcription process. The protein's interaction with various host factors and its role in viral maturation also make it a potential target for antiviral therapies. Thus, abnormalities or mutations in the Gag protein can lead to defective virus particles and influence the course of HIV infection.

Bioapplications of GAG

HIV Gag protein plays a critical role in the assembly and release of HIV particles, and it serves as a target for developing therapeutics and vaccines. The Gag protein can be engineered to display high antigen density on virus-like particles (VLPs), which can induce strong antibody-dependent immune responses. This approach is being explored for HIV vaccine development, as Gag-based VLPs have shown the potential to elicit potent immune responses. The application of Gag in vaccine design and as a therapeutic target makes it a significant protein in the context of HIV-related research and treatment strategies.

Case Study 1: Zaret G. Denieva, 2024

HIV Gag protein is crucial for virus assembly and membrane deformation during the formation of immature virions. Although Gag expression triggers virus-like particle budding, the mechanism of membrane curvature induction is not completely clear. This study using lipid nanotubes revealed that Gag, even without myristoylation, can significantly alter membrane shape, especially in the presence of charged lipids like PI(4,5)P2. Gag reduces interfacial tension, similar to amphipathic peptides, and a region of Gag resembling magainin-1 could be responsible for this effect. Here Gag acts like a surfactant, softening the membrane and reducing the energy required for membrane bending, providing a unified mechanism for protein-induced membrane curvature.

Fig1. Typical kinetics of 330 nM Gag adsorption at the outer leaflet of the nanotubes with the lipid composition A.

Fig2. Hydrophobic cluster analysis (HCA) of the Gag CA-SP1 junction region (upper) and magainin-1 (lower).

Case Study 2: Nario Tomishige, 2023

The process by which human immunodeficiency virus type 1 (HIV-1) enriches its lipid envelope with host cell sphingomyelin and cholesterol is not fully understood. This study reveals the interaction between HIV-1 Gag protein and host cell lipids using advanced microscopy and specific lipid-binding probes. Here Gag in the plasma membrane's inner leaflet interacts with and enlarges sphingomyelin-rich domains, while also restricting their mobility. Gag multimerization further clusters these lipid domains in a curvature-dependent manner. These findings suggest that Gag plays a role in organizing and reorganizing existing lipid domains during viral assembly.

Fig3. Averaged recovery curves of EGFP-NT-Lys from three independent experiments.

Fig4. The mean diameters Gag-mEos4b derivatives domains in each cell.

gag has several biochemical functions, for example, . Some of the functions are cooperated with other proteins, some of the functions could acted by gag itself. We selected most functions gag had, and list some proteins which have the same functions with gag. You can find most of the proteins on our site.

gag has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with gag here. Most of them are supplied by our site. Hope this information will be useful for your research of gag.