Gp41

GP41
Example crystal structures of HIV-1 envelope glycoprotein Gp41
Identifiers
Symbol	GP41
Pfam	PF00517
InterPro	IPR000328
SCOP	2siv
SUPERFAMILY	2siv
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Gp41 also known as glycoprotein 41 is a subunit of the envelope protein complex of retroviruses, including human immunodeficiency virus (HIV). Gp41 is a transmembrane protein that contains several sites within its ectodomain that are required for infection of host cells. As a result of its importance in host cell infection, it has also received much attention as a potential target for HIV vaccines.

Gp41 is coded with gp120 as one gp160 by the env gene of HIV. Gp160 is then extensively glycosylated and proteolytically cleaved by furin, a host cellular protease. The high glycosylation of the env coded glycoproteins allows them to escape the human body's immune system. In contrast to gp120, however, gp41 is less glycosylated and more conserved (less prone to genetic variations). Once gp160 has been cleaved into its individual subunits, the subunits are then associated non-covalently on the surface of the viral envelope.

Gp41 and gp120, when non-covalently bound to each other, are referred to as the envelope spike complex and are formed as a heterotrimer of three gp41 and three gp120. These complexes found on the surface of HIV are responsible for the attachment, fusion, and ultimately the infection of host cells. The structure is cage-like with a hollow center that inhibits antibody access. While gp120 sits on the surface of the viral envelope, gp41 is the transmembrane portion of the spike complex with a portion of the glycoprotein buried within the viral envelope at all times.

Gp41 has three prominent regions within the sequence: the ectodomain, the transmembrane domain, and the cytoplasmic domain. The ectodomain, which comprises residues 511-684, can be further broken down into the fusion peptide region (residues 512-527), the helical N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR). In addition to these regions, there is also a loop region that contains disulfide bonds that stabilize the hairpin structure (the folded conformation of gp41) and a region called the membrane proximal external region (MPER) which contains kinks that are antigen target regions. The fusion peptide region is normally buried or hidden by the non-covalent interactions between gp120 and gp41, at a point which looks torus-like. This prevents the fusion peptide from interacting with other regions that are not its intended target region.