3WE1

Crystal structure of Dengue 4 Envelope protein domain III (ED3)

Summary for 3WE1

• Entry DOI: 10.2210/pdb3we1/pdb
• Descriptor: Envelope protein E (2 entities in total)
• Functional Keywords: immunoglobulin like domain, cell surface receptor binding, represent epitope, virus surface, structural protein, immune system
• Biological source: Dengue virus type 4 (DENV-4)
• Cellular location: Capsid protein C: Virion . Peptide pr: Secreted . Small envelope protein M: Virion membrane ; Multi-pass membrane protein . Envelope protein E: Virion membrane ; Multi-pass membrane protein . Non-structural protein 1: Secreted . Non-structural protein 2A: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Serine protease subunit NS2B: Host endoplasmic reticulum membrane; Multi-pass membrane protein . Serine protease NS3: Host endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side . Non-structural protein 4A: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . Non-structural protein 4B: Host endoplasmic reticulum membrane ; Multi-pass membrane protein . RNA-directed RNA polymerase NS5: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side: P09866
• Total number of polymer chains: 2
• Total formula weight: 22954.16

Authors

Elahi, M.,Islam, M.M.,Noguchi, K.,Yohda, M.,Toh, H.,Kuroda, Y. (deposition date: 2013-06-27, release date: 2014-01-22, Last modification date: 2024-11-20)

Primary citation

Elahi, M.,Islam, M.M.,Noguchi, K.,Yohda, M.,Toh, H.,Kuroda, Y.
Computational prediction and experimental characterization of a "size switch type repacking" during the evolution of dengue envelope protein domain III (ED3).
Biochim.Biophys.Acta, 1844:585-592, 2014

PubMed Abstract: Dengue viruses (DEN) are classified into four serotypes (DEN1-DEN4) exhibiting high sequence and structural similarities, and infections by multiple serotypes can lead to the deadly dengue hemorrhagic fever. Here, we aim at characterizing the thermodynamic stability of DEN envelope protein domain III (ED3) during its evolution, and we report a structural analysis of DEN4wt ED3 combined with a systematic mutational analysis of residues 310 and 387. Molecular modeling based on our DEN3 and DEN4 ED3 structures indicated that the side-chains of residues 310/387, which are Val(310)/Ile(387) and Met(310)/Leu(387) in DEN3wt and DEN4wt, respectively, could be structurally compensated, and that a "size switch type repacking" might have occurred at these sites during the evolution of DEN into its four serotypes. This was experimentally confirmed by a 10°C and 5°C decrease in the thermal stability of, respectively, DEN3 ED3 variants with Met(310)/Ile(387) and Val(310)/Leu(387), whereas the variant with Met(310)/Leu(387), which contains a double mutation, had the same stability as the wild type DEN3. Namely, the Met310Val mutation should have preceded the Leu387Ile mutation in order to maintain the tight internal packing of ED3 and thus its thermodynamic stability. This view was confirmed by a phylogenetic reconstruction indicating that a common DEN ancestor would have Met(310)/Leu(387), and the intermediate node protein, Val(310)/Leu(387), which then mutated to the Val(310)/Ile(387) pair found in the present DEN3. The hypothesis was further confirmed by the observation that all of the present DEN viruses exhibit only stabilizing amino acid pairs at the 310/387 sites.

PubMed: 24373879
DOI: 10.1016/j.bbapap.2013.12.013

Experimental method

X-RAY DIFFRACTION (2.278 Å)