| RESEARCH HIGHLIGHTS |
that his team has used AFM to investigate mac- romolecular behavior for about 25 years. The researchers anchored a few protein molecules to AFM probes approximating one micrometer across and assessed their adhesion force to charged surfaces at well-defined pH values while pulling the probes off these surfaces. After validating this approach for various well-known proteins, the team tackled the pI
value of the footprint protein. According to Vancso, this protein stimulates the attachment of a larva, which triggers colonization and further build-up by other larvae. The protein exhibited a pI value of 9.6 to 9.7, consistent with its positive charge in seawater and its adhesiveness to the negatively charged immersed surfaces. This proof-of-concept experiment
minimized protein amount requirements. “We
hope that we contributed to the solving of this notoriously difficult and very essential issue,” says Vancso. They expect that protein scientists will adopt their technique.
1. Guo, S., Zhu, X., Jańczewski, D., Lee, S. S. C., He, T. et al. Measuring protein isoelectric points by AFM-based force spectroscopy using trace amounts of sample. Nature Nanotechnology 11, 817–823 (2016).
Dengue
MOLECULAR 'MOVIE' REELS VIRAL ENVELOPE INTO SHAPE
COMPUTER SIMULATIONS REVEAL EVERY CURVE OF THE DENGUE CAPSULE
The near-spherical outer structure of the dengue virus has been recreated in remarkable detail by a team of bioinformaticians in Singapore1. The virtual model could show researchers how the virus fuses with and infects human cells at the molecular level. “We want to understand the relationship between struc- ture and dynamics along the pathway of fusion
A simulation of the dengue virus fusing with the mem- brane of a vesicle inside a cell.
and infection, with a view to developing new vaccines and therapies,” says Peter Bond, who, together with Chandra Verma, led the study at the A*STAR Bioinformatics Institute. Dengue is a mosquito-borne virus that
infects an estimated 400 million people a year, resulting in 21,000 deaths worldwide. It is a flavivirus — the same family as the Zika
virus, Japanese encephalitis and yellow fever. Flaviviruses share a common structure: a sin- gle-stranded RNA genome encased in a capsule made up of a fatty lipid sandwich stuffed with proteins called envelopes and membranes. Once inside human cells, the smooth outer
shell of the dengue virus forms spikes and fuses with the membrane of transport vesicles called endosomes, infecting the cell through the release of the viral genome. Researchers are particularly interested in how the external envelope proteins facilitate this process. “These proteins are the first thing to come into contact with our immune system,” says Bond. “If we are going to protect ourselves, we need to recognize and, ideally, neutralize them.” The problem with standard experimental
techniques such as cryoelectron microscopy for visualizing biological systems is that they can only detect ordered, uniform solids. Dengue’s lipid membranes, however, are in a free-flowing state, somewhere between solid and liquid. Bond and Verma’s teams overcame this hurdle using computational modeling, which applies
50 A*STAR RESEARCH ISSUE 6 | JANUARY – MARCH 2017
© 2017 A*STAR Bioinformatics Institute
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