PMID: 19737401

 

    Legend: Gene, Sites

Title : The formation of cysteine-linked dimers of BST-2 / tetherin is important for inhibition of HIV-1 virus release but not for sensitivity to Vpu

Abstract :
  1. BACKGROUND: The Human Immunodeficiency virus type 1 ( HIV-1) Vpu protein enhances virus release from infected cells and induces proteasomal degradation of CD4
  2. Recent work identified BST-2 / CD317 as a host factor that inhibits HIV-1 virus release in a Vpu sensitive manner
  3. A current working model proposes that BST-2 inhibits virus release by tethering viral particles to the cell surface thereby triggering their subsequent endocytosis
  4. RESULTS: Here we defined structural properties of BST-2 required for inhibition of virus release and for sensitivity to Vpu
  5. We found that BST-2 is modified by N-linked glycosylation at two sites in the extracellular domain
  6. However, N-linked glycosylation was not important for inhibition of HIV-1 virus release nor did it affect surface expression or sensitivity to Vpu
  7. Rodent BST-2 was previously found to form cysteine-linked dimers
  8. Analysis of single, double, or triple cysteine mutants revealed that any one of three cysteine residues present in the BST-2 extracellular domain was sufficient for BST-2 dimerization , for inhibition of virus release, and sensitivity to Vpu
  9. In contrast, BST-2 lacking all three cysteines in its ectodomain was unable to inhibit release of wild type or Vpu-deficient HIV-1 virions
  10. This defect was not caused by a gross defect in BST-2 trafficking as the mutant protein was expressed at the cell surface of transfected 293T cells and was down-modulated by Vpu similar to wild type BST-2
  11. CONCLUSION: While BST-2 glycosylation was functionally irrelevant, formation of cysteine-linked dimers appeared to be important for inhibition of virus release
  12. However lack of dimerization did not prevent surface expression or Vpu sensitivity of BST-2 , suggesting Vpu sensitivity and inhibition of virus release are separable properties of BST-2
Output (sent_index, trigger, protein, sugar, site):
  • 9. cysteines, , -, its ectodomain, ectodomain
Output(Part-Of) (sent_index, protein, site):
  • 8. BST-2, domain
*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

 

Protein NCBI ID SENTENCE INDEX
Vpu 155945 2,4,6,8,10,12
CD4 920 1
CD317 684 2