Characterization of the papillomavirus α1E2 peptide unfolded to folded transition upon DNA binding

Giesel, Guilherme Menegon; Lima, Luís Maurício T.R.; Faber-Barata, Joana; Guimarães, Jorge Almeida; Verli, Hugo

doi:10.1016/j.febslet.2008.09.041

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Volume 582, Issue 25 , Pages 3619-3624, 29 October 2008

Characterization of the papillomavirus α₁E2 peptide unfolded to folded transition upon DNA binding

Edited by Robert B. Russell

Guilherme Menegon Giesel
- Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Av Bento Gonçalves 9500, CP 15005, Porto Alegre 91500-970, RS, Brazil
Luís Maurício T.R. Lima
- Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil
Joana Faber-Barata
- Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil
- Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil
Jorge Almeida Guimarães
- Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Av Bento Gonçalves 9500, CP 15005, Porto Alegre 91500-970, RS, Brazil
Hugo Verli
- Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Av Bento Gonçalves 9500, CP 15005, Porto Alegre 91500-970, RS, Brazil
- Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Av Ipiranga 2752, Porto Alegre 90610-000, RS, Brazil
- Corresponding author. Address: Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Av Bento Gonçalves 9500, CP 15005, Porto Alegre 91500-970, RS, Brazil. Fax: +55 51 3316 7309.

Received 26 May 2008; received in revised form 11 September 2008; accepted 22 September 2008. published online 30 September 2008.

Abstract

Transcriptional regulation depends on sequence-specific binding of regulatory proteins to their responsive elements in viral DNA. The papillomavirus E2 protein binds to DNA through the consensus sequence ACCG-NNNN-CGGT, activating or inhibiting viral replication. Through molecular dynamics simulations we were able to characterize the role of the DNA molecule on E2 binding region (named α₁E2) conformation, acquiring structural insights for previous works suggesting an unfolded to folded transition upon α₁E2 complexation to DNA. Moreover, the results indicate sites to guide the design of α₁E2 synthetic derivatives to inhibit the HPV infection.

Keywords: Molecular dynamics, Papillomavirus, E2 protein, DNA structure, Induced fit