RSS

PDB:2NY7

Protein Name

HIV-1 enverope protein gp120/b12 complex

Species

Human

Biological Context

Human immunodeficiency virus (HIV) infects human immune cells, and causes the significant deficiency of the immune system by destroying it. The origin of this virus is considered to be the simian immunodeficiency virus(SIV) having acquired the infection capability to human by mutation. The cell surface of HIV is covered with envelope-protein (ENV) like many spikes. ENV consists of three transmembrane protein gp41 and three exocellular protein gp120(PDB:1GC1). To facilitate viral entry, the gp120 binds to the cell-surface CD4 receptor, then alter its conformation largely. Thereby, bp120 bind to CCR5 and CXCR4 which are co-receptor. Next, HIV fuses with the host cell membrane by regulation of gp41. And RNA which is the genome of HIV, together with a series of enzyme, are sent into the inside the host cell. RNA is reverse-transcribed to the DNA by the reverse transcriptase (PDB:3HVT), and it is embedded in the DNA of the host cell. Through transcription and translation of the host cell DNA, HIV proliferates, and are released into outside cell by breaking the cell membrane. In order to stop such a subversive activity of HIV, the first shortcut is preventing HIV to bind with CD4 receptor of immune cells. For this purpose, we have to design the antibody specifically binding with ENV. However, ENV tend to mutate and change the conformation constantly. This property makes the designing of the antibody difficult. By Zhou and others' research, it turned out that before binding to CD4 receptor, the CD4-binding region is exposed to surface. This region is well conserved, and hard to make conformational changes. That is to say, this region is a weak point of HIV. Furthermore, b12 antibody, which is a SIV preventive medicine of simian, can bind to this region.

HIV
(Fig.1) HIV cross-section diagram

Structure Description

2ny72ny7_x2ny7_y

The structures shown first in (Fig.2) is gp120 of HIV-1 complexed with CD4 receptor. gp120 consists of two domains; an inner domain and an outer domain. The outer domain has two barrel structures. CD4 receptor is bonded with the loop near the juncture of two barrels (purple loop of Fig.2). Next, the structure shown in (Fig .3) is gp120 complexed with b12 antibody. This gp120 is not a wild-type, but two disulfide bonds and three amino acid residues substitution are conducted. This is for the purpose of fixing gp120 in the state of binding to CD4 receptor. It was proved that three CDR loops (CDR-H1, H2, H3) of the H-chain of b12 antibody bind with the almost same region as CD4 receptor. However, CD4 receptor and b12 interact with the CD4-binding loop in a different manner. b12 uses all three of its CDRs loops to grasp virtually all surface-exposed portions of the loop. In contrast, CD4 receptor only binds to one side of the loop. The knowledge acquired this time must greatly be useful for development of the vaccine which induces the antibody targeting gp120.

CD4
(Fig.2) gp120/CD4-receptor complex
b12
(Fig.3) gp120/b12 complex

Protein Data Bank (PDB)

References

Source

Zhou, T. Xu, L. Dey, B. Hessell, A.J. Van Ryk, D. Xiang, S.H. Yang, X. Zhang, M.Y. Zwick, M.B. Arthos, J. Burton, D.R. Dimitrov, D.S. Sodroski, J. Wyatt, R. Nabel, G.J. Kwong, P.D.; "Structural definition of a conserved neutralization epitope on HIV-1 gp120."; Nature; (2007) 445:732-737 PubMed:17301785.

Others

  • xPSSS:2NXY gp120/CD4/17b complex : wild-type gp120
  • xPSSS:2NXZ gp120/CD4/17b complex : 1 residue mutant(F2) gp120
  • xPSSS:2NX0 gp120/CD4/17b complex : 1 disulfide(Ds1), 3 residues mutant(F123) gp120
  • xPSSS:2NX1 gp120/CD4/17b complex : 1 disulfide(Ds2), 1 residue mutant(F2) gp120
  • xPSSS:2NX2 gp120/CD4/17b complex : 1 disulfide(Ds3), 1 residue mutant(F2) gp120
  • xPSSS:2NX3 gp120/CD4/17b complex : 1 disulfide(Ds4), 1 residue mutant(F2) gp120
  • xPSSS:2NX4 gp120/CD4/17b complex : 1 disulfide(Ds5), 1 residue mutant(F2) gp120
  • xPSSS:2NX5 gp120/CD4/17b complex : 2 disulfides(Ds12), 3 residues mutant(F123) gp120
  • xPSSS:2NX6 gp120/CD4/17b complex : 3 disulfide(Ds123), 2 residues mutant(F12) gp120

author: Jun-ichi Ito


Japanese version:PDB:2NY7