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2030-01-01
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THE DISORDERED N-TERMINAL REGION OF DENGUE VIRUS CAPSID PROTEIN CONTAINS A LIPID-DROPLET-BINDING MOTIF
Martins, Ivo C. et al. | Date Issued: 2012
Author
Martins, Ivo C.
Gomes Neto, Francisco
Faustino, André F.
Carvalho, Filomena A.
Carneiro, Fabiana A.
Bozza, Patrícia T.
Borges, Ronaldo Mohana
Castanho, Miguel A. R. B.
Almeida, Fabio C. L.
Santos, Nuno C.
Poian, Andrea T. da
Affilliation
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo De Meis. Rio de Janeiro, RJ, Brasil / Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular. Lisboa, Portugal.
Universidade Federal do Rio de Janeiro. Centro Nacional de Ressonância Magnética Nuclear. Rio de Janeiro, RJ, Brasil / National Institute of Structural Biology and Bioimage. Rio de Janeiro, RJ, Brazil.
Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular. Lisboa, Portugal.
Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular. Lisboa, Portugal.
Universidade Federal do Rio de Janeiro. Polo Avançado de Xerém. Duque de Caxias, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Bioffísica Carlos Chagas Filho. Laboratório de Genômica Estrutural. Rio de Janeiro, RJ, Brasil.
Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular. Lisboa, Portugal.
Universidade Federal do Rio de Janeiro. Centro Nacional de Ressonância Magnética Nuclear. Rio de Janeiro, RJ, Brasil / National Institute of Structural Biology and Bioimage. Rio de Janeiro, RJ, Brazil.
Universidade de Lisboa. Faculdade de Medicina. Instituto de Medicina Molecular. Lisboa, Portugal.
Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo De Meis. Rio de Janeiro, RJ, Brasil.
Abstract
Dengue is the major arthropod-borne human viral disease, for which no vaccine or specific treatment is available. We used NMR, zeta potential measurements and atomic force microscopy to study the structural features of the interaction between dengue virus C (capsid) protein and LDs (lipid droplets), organelles crucial for infectious particle formation. C protein-binding sites to LD were mapped, revealing a new function for a conserved segment in the N-terminal disordered region and indicating that conformational selection is involved in recognition. The results suggest that the positively charged N-terminal region of C protein prompts the interaction with negatively charged LDs, after which a conformational rearrangement enables the access of the central hydrophobic patch to the LD surface. Taken together, the results allowed the design of a peptide with inhibitory activity of C protein-LD binding, paving the way for new drug development approaches against dengue.
Keywords in Portuguese
Dengue
Ressonância Magnética
Força atômica microscópica
Proteína da cápside
Vírus da Dengue
Gotícula lipídica
 
Keywords
atomic force microscopy (AFM)
capsid protein
conformational selection, dengue virus (DENV
intrinsically disordered protein, lipid droplet
NMR
 
Publisher
Biochemical Society
Citation
MARTINS, Ivo C. et al. The disordered N-terminal region of dengue virus capsid protein contains a lipid-droplet-binding motif. Biochem. J., v. 444, p. 405–415, 2012.
DOI
10.1042/BJ20112219
ISSN
0264-6021