Hiv env proteins

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Introduction

Human Immunodeficiency Virus (HIV) is a retrovirus/lentivirus that expresses a spike protein on its viral envelope (Env). "The envelope protein is synthesized as a precursor, gp160, which trimerizes and undergoes cleavage into two noncovalently associated fragments, the receptor-binding fragment gp120 and the fusion fragment gp41" ^[1]. Thus, Env is a heterodimer consisting of gp120 and gp41 and forms trimers on the surface of the viral membrane. As "the sole antigen on the virion surface," an understanding of Env (gp 120 & 41) and the conformational changes that occur in gp120 and gp41 during binding and fusion, respectively, is necessary in developing new fusion inhibitors and possible vaccines ^{[1] [2]}. The protein structure shown on the right is the gp120 portion of Env in its unbound trimer state ^[2].

Env Structure

The viral Env protein, as mentioned above, is composed of gp120 and gp41 that forms trimers on the viral membrane surface. The image to the right, displays the undecorated Env trimer. Within the gp120 monomeric proteins are variable loops that undergo conformational changes that support binding or restrict binding of receptors such as CD4 or antibodies. Two important loops in this regard are the V1/V2 loops. The V1/V2 loops are located at the apex of the structure in the center of the three monomeric gp120 proteins. Depending on the gp120 conformation changes, the three gp41 transmembrane proteins, located beneath the gp120 surface proteins (located by the white arrow in F2.b), will undergo "irreversible refolding," bringing the viral membrane and host cell membrane closer together, consequently inducing fusion ^[1].

gp120 Binding

gp120 is responsible for the binding of HIV to CD4 cells. "Binding of gp120 to the primary receptor CD4 and coreceptor (for example, CCR5 and CXCR4) induces large conformational changes, which then trigger dissociation of gp120 and a cascade of refolding events in gp41" ^[1].