title: The disordered N-terminal region of dengue virus capsid protein contains a lipid-droplet-binding motif.
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.
authors.affiliation: Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil.
authors.forename: Ivo C
authors.initials: IC
authors.lastname: Martins
authors.forename: Francisco
authors.initials: F
authors.lastname: Gomes-Neto
authors.forename: André F
authors.initials: AF
authors.lastname: Faustino
authors.forename: Filomena A
authors.initials: FA
authors.lastname: Carvalho
authors.forename: Fabiana A
authors.initials: FA
authors.lastname: Carneiro
authors.forename: Patricia T
authors.initials: PT
authors.lastname: Bozza
authors.forename: Ronaldo
authors.initials: R
authors.lastname: Mohana-Borges
authors.forename: Miguel A R B
authors.initials: MA
authors.lastname: Castanho
authors.forename: Fábio C L
authors.initials: FC
authors.lastname: Almeida
authors.forename: Nuno C
authors.initials: NC
authors.lastname: Santos
authors.forename: Andrea T
authors.initials: AT
authors.lastname: Da Poian
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D003716:Dengue Virus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011487:Protein Conformation; D055672:Static Electricity
chemical_list: D036022:Capsid Proteins; D008055:Lipids; D010446:Peptide Fragments