The disordered N-terminal region of dengue virus capsid protein contains a lipid-droplet-binding motif

©The Authors Journal compilation ©2012 Biochemical Society - 'The final version of record is available at http://www.biochemj.org/bj/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.This work was supported by the European Union 7th Framework Programme PEOPLE IRSES (International Research Staff Exchange Scheme) project MEMPEPACROSS, the National Institute of Science and Technology in Dengue (INCTD, Brazil), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil), the Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, Brazil), the Fundação para a Ciência e a Tecnologia (FCT)–Ministério da Educação e Ciência (MEC) (Portugal) [grant number PTDC/QUI-BIQ/112929/2009], the Fundação Calouste Gulbenkian (Portugal), and FCT–Fundação Coordenação de Aperfeiçoamento do Pessoal de Nível Superior (CAPES) Portugal–Brazil joint co-operation projects. I.C.M. is the recipient of consecutive postdoctoral funding from a Marie Curie International Outgoing Fellowship [grant number MC-IOF237373] and FCT postdoctoral fellowships [grant numbers SFRH/BPD/46324/2008 and SFRH/BPD/74287/2010