Utilize este identificador para referenciar este registo: http://hdl.handle.net/10451/23429
Título: Understanding Dengue virus capsid protein disordered N‑Terminus and pep14-23-based inhibition
Autor: Faustino, André F.
Guerra, Gabriela M.
Huber, Roland G.
Hollmann, Axel
Domingues, Marco M.
Barbosa, Glauce M.
Enguita, Francisco J.
Bond, Peter J.
Castanho, Miguel A. R. B.
Poian, Andrea T. da
Almeida, Fabio C. L.
Data: 2015
Editora: American Chemical Society
Citação: ACS Chem. Biol. 2015, 10, 517−526
Resumo: Dengue virus (DENV) infection affects millions of people and is becoming a major global disease for which there is no specific available treatment. pep14-23 is a recently designed peptide, based on a conserved segment of DENV capsid (C) protein. It inhibits the interaction of DENV C with host intracellular lipid droplets (LDs), which is crucial for viral replication. Combining bioinformatics and biophysics, here, we analyzed pep14-23 structure and ability to bind different phospholipids, relating that information with the full-length DENV C. We show that pep14-23 acquires α-helical conformation upon binding to negatively charged phospholipid membranes, displaying an asymmetric charge distribution structural arrangement. Structure prediction for the N-terminal segment reveals four viable homodimer orientations that alternatively shield or expose the DENV C hydrophobic pocket. Taken together, these findings suggest a new biological role for the disordered Nterminal region, which may function as an autoinhibitory domain mediating DENV C interaction with its biological targets. The results fit with our current understanding of DENV C and pep14-23 structure and function, paving the way for similar approaches to understanding disordered proteins and improved peptidomimetics drug development strategies against DENV and similar Flavivirus infections.
Descrição: © 2014 American Chemical Society
Peer review: yes
URI: http://hdl.handle.net/10451/23429
DOI: 10.1021/cb500640t
ISSN: 1554-8929
Versão do Editor: http://pubs.acs.org/doi/abs/10.1021/cb500640t
Aparece nas colecções:IMM - Artigos em Revistas Internacionais
FM-IB-Artigos em Revistas Internacionais

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