The gp120 protein is a glycoprotein found on the outer surface of the Human Immunodeficiency Virus (HIV). A glycoprotein is a protein that has sugar molecules, or glycans, attached to it. The name “gp120” comes from its approximate molecular weight of 120 kilodaltons (kDa). This protein was first identified in 1984 by Professors Tun-Hou Lee and Myron “Max” Essex, and its study is fundamental to understanding the virus.
Understanding gp120
Gp120 is a component of the outer envelope of the Human Immunodeficiency Virus. These sugar components contribute to its complex structure and can help the virus evade the immune system. The protein is non-covalently linked to another viral envelope protein, gp41, forming a complex that protrudes from the viral membrane. Three gp120 and three gp41 molecules combine to create what is known as an envelope spike, which is the primary structure mediating the virus’s interaction with host cells. Gp120 itself has a complex and variable structure, featuring an outer domain, an inner domain, and a bridging sheet.
How gp120 Facilitates HIV Entry
Gp120 mediates the virus’s attachment to human immune cells. The process begins when gp120 specifically recognizes and binds to the CD4 receptor, a protein found on the surface of T-helper cells and other immune cells.
Upon binding to CD4, gp120 undergoes a significant change in its shape, known as a conformational change. This alteration exposes a new binding site on gp120 for co-receptors, which are also located on the surface of the host cell. The most common co-receptors are CCR5 and CXCR4, and the specific co-receptor used can influence which cell types the virus infects.
The binding of gp120 to these co-receptors triggers further conformational changes in both gp120 and gp41. These changes ultimately lead to the insertion of a fusion peptide from gp41 into the host cell membrane. This action pulls the viral and host cell membranes together, facilitating their fusion and allowing the viral genetic material to enter the host cell and initiate infection.
Targeting gp120 for Medical Advancements
Because gp120 is the primary point of contact between HIV and human cells, it is a significant target for developing new medical interventions. Its exposed location on the viral surface makes it accessible for therapeutic agents. Researchers are particularly interested in gp120 as an antigen, making it a focus for vaccine development.
Understanding gp120’s structure and function has led to the development of entry inhibitor drugs. These drugs work by blocking the virus from entering cells, often by interfering with the interaction between gp120 and host cell receptors. For example, some attachment inhibitors bind to gp120 itself, preventing its initial interaction with the CD4 receptor.
Despite its potential as a target, developing effective interventions against gp120 presents challenges. The protein’s high variability allows the virus to mutate rapidly and “hide” vulnerable regions from the immune system. This variability complicates the design of vaccines that can elicit broadly neutralizing antibodies.