HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Disulfide bond that constrains the HIV-1 gp120 V3 domain is cleaved by thioredoxin.

Abstract
A functional disulfide bond in both the HIV envelope glycoprotein, gp120, and its immune cell receptor, CD4, is involved in viral entry, and compounds that block cleavage of the disulfide bond in these proteins inhibit HIV entry and infection. The disulfide bonds in both proteins are cleaved at the cell surface by the small redox protein, thioredoxin. The target gp120 disulfide and its mechanism of cleavage were determined using a thioredoxin kinetic trapping mutant and mass spectrometry. A single disulfide bond was cleaved in isolated and cell surface gp120, but not the gp160 precursor, and the extent of the reaction was enhanced when gp120 was bound to CD4. The Cys(32) sulfur ion of thioredoxin attacks the Cys(296) sulfur ion of the gp120 V3 domain Cys(296)-Cys(331) disulfide bond, cleaving the bond. Considering that V3 sequences largely determine the chemokine receptor preference of HIV, we propose that cleavage of the V3 domain disulfide, which is facilitated by CD4 binding, regulates chemokine receptor binding. There are 20 possible disulfide bond configurations, and, notably, the V3 domain disulfide has the same unusual -RHStaple configuration as the functional disulfide bond cleaved in CD4.
AuthorsIman Azimi, Lisa J Matthias, Rob J Center, Jason W H Wong, Philip J Hogg
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 285 Issue 51 Pg. 40072-80 (Dec 17 2010) ISSN: 1083-351X [Electronic] United States
PMID20943653 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • CD4 Antigens
  • Disulfides
  • HIV Envelope Protein gp120
  • Receptors, Chemokine
  • gp120 protein, Human immunodeficiency virus 1
  • Thioredoxins
Topics
  • CD4 Antigens (genetics, metabolism)
  • Disulfides (metabolism)
  • HEK293 Cells
  • HIV Envelope Protein gp120 (genetics, metabolism)
  • HIV-1 (genetics, metabolism)
  • Humans
  • Kinetics
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Chemokine (genetics, metabolism)
  • Thioredoxins (genetics, metabolism)
  • Virus Internalization

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: