Functional interaction between the cytoplasmic leucine-zipper domain of HIV-1 gp41 and p115-RhoGEF

H. Zhang, L. Wang, S. Kao, I. P. Whitehead, Matthew J Hart, B. Liu, K. Duus, K. Burridge, C. J. Der, L. Su

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

The long cytoplasmic tail of the human immunodeficiency virus (HIV)-I transmembrane protein gp41 (gp41C) is implicated in the replication and cytopathicity of HIV-1 [1]. Little is known about the specific functions of gp41C, however. HIV-1 or simian immunodeficiency virus (SIV) mutants with defective gp41C have cell-type- or species-dependent phenotypes [2-6]. Thus, host factors are implicated in mediating the functions of gp41C. We report here that gp41C interacted with the carboxy-terminal regulatory domain of p115-RhoGEF [7], a specific guanine nucleotide exchange factor (GEF) and activator of the RhoA GTPase, which regulates actin stress fiber formation, activation of serum response factor (SRF) and cell proliferation [8,9]. We demonstrate that gp41C inhibited p115-mediated actin stress fiber formation and activation of SRF. An amphipathic helix region with a leucine-zipper motif in gp41C is involved in its interaction with p115. Mutations in gp41C leading to loss of interaction with p115 impaired HIV-1 replication in human T cells. These findings suggest that an important function of gp41C is to modulate the activity of p115-RhoGEF and they thus reveal a new potential anti-HIV-1 target.

Original languageEnglish (US)
Pages (from-to)1271-1274
Number of pages4
JournalCurrent Biology
Volume9
Issue number21
StatePublished - Nov 4 1999
Externally publishedYes

Fingerprint

Rho Guanine Nucleotide Exchange Factors
Leucine Zippers
leucine zipper
Human immunodeficiency virus 1
Viruses
HIV-1
Serum Response Factor
Stress Fibers
actin
GTP Phosphohydrolase Activators
Actins
Simian immunodeficiency virus
Guanine Nucleotide Exchange Factors
Simian Immunodeficiency Virus
transmembrane proteins
Human immunodeficiency virus
guanosinetriphosphatase
Virus Replication
Chemical activation
Tail

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Zhang, H., Wang, L., Kao, S., Whitehead, I. P., Hart, M. J., Liu, B., ... Su, L. (1999). Functional interaction between the cytoplasmic leucine-zipper domain of HIV-1 gp41 and p115-RhoGEF. Current Biology, 9(21), 1271-1274.

Functional interaction between the cytoplasmic leucine-zipper domain of HIV-1 gp41 and p115-RhoGEF. / Zhang, H.; Wang, L.; Kao, S.; Whitehead, I. P.; Hart, Matthew J; Liu, B.; Duus, K.; Burridge, K.; Der, C. J.; Su, L.

In: Current Biology, Vol. 9, No. 21, 04.11.1999, p. 1271-1274.

Research output: Contribution to journalArticle

Zhang, H, Wang, L, Kao, S, Whitehead, IP, Hart, MJ, Liu, B, Duus, K, Burridge, K, Der, CJ & Su, L 1999, 'Functional interaction between the cytoplasmic leucine-zipper domain of HIV-1 gp41 and p115-RhoGEF', Current Biology, vol. 9, no. 21, pp. 1271-1274.
Zhang H, Wang L, Kao S, Whitehead IP, Hart MJ, Liu B et al. Functional interaction between the cytoplasmic leucine-zipper domain of HIV-1 gp41 and p115-RhoGEF. Current Biology. 1999 Nov 4;9(21):1271-1274.
Zhang, H. ; Wang, L. ; Kao, S. ; Whitehead, I. P. ; Hart, Matthew J ; Liu, B. ; Duus, K. ; Burridge, K. ; Der, C. J. ; Su, L. / Functional interaction between the cytoplasmic leucine-zipper domain of HIV-1 gp41 and p115-RhoGEF. In: Current Biology. 1999 ; Vol. 9, No. 21. pp. 1271-1274.
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