Tag Archives: Publications

Structure of the thermally stable Zika virus

by Victor A. Kostyuchenko, Elisa X. Y. Lim, Shuijun Zhang, Guntur Fibriansah, Thiam-Seng Ng, Justin S. G. Ooi, Jian Shi & Shee-Mei Lok

Nature (2016) doi:10.1038/nature17994  Published online 19 April 2016

Zika virus (ZIKV), formerly a neglected pathogen, has recently been associated with microcephaly in fetuses1, and with Guillian–Barré syndrome in adults2. Here we present the 3.7 Å resolution cryo-electron microscopy structure of ZIKV, and show that the overall architecture of the virus is similar to that of other flaviviruses. Sequence and structural comparisons of the ZIKV envelope (E) protein with other flaviviruses show that parts of the E protein closely resemble the neurovirulent West Nile and Japanese encephalitis viruses, while others are similar to dengue virus (DENV). However, the contribution of the E protein to flavivirus pathobiology is currently not understood. The virus particle was observed to be structurally stable even when incubated at 40 °C, in sharp contrast to the less thermally stable DENV3. This is also reflected in the infectivity of ZIKV compared to DENV serotypes 2 and 4 (DENV2 and DENV4) at different temperatures. The cryo-electron microscopy structure shows a virus with a more compact surface. This structural stability of the virus may help it to survive in the harsh conditions of semen4, saliva5 and urine6. Antibodies or drugs that destabilize the structure may help to reduce the disease outcome or limit the spread of the virus.

Read online: Nature.

Transcriptional enhancement of Smn levels in motoneurons is crucial for proper axon morphology in zebrafish

by Zoltan Spiro, Angela Koh, Shermaine Tay, Kelvin See, Christoph Winkler

Scientific Reports 6, 2016  (07 June 2016)

An unresolved mystery in the field of spinal muscular atrophy (SMA) is why a reduction of the ubiquitously expressed Smn protein causes defects mostly in motoneurons. We addressed the possibility that this restricted vulnerability stems from elevated Smn expression in motoneurons. To explore this, we established an ex vivo zebrafish culture system of GFP-marked motoneurons to quantitatively measure Smn protein and smn mRNA levels as well as promoter activity in motoneurons versus other cell types. Importantly, we uncovered that Smn levels are elevated in motoneurons by means of transcriptional activation. In addition, we identified the ETS family transcription factor Etv5b to be responsible for increased smn transcription in motoneurons. Moreover, we established that the additional supply of Smn protein in motoneurons is necessary for proper axonogenesis in a cell-autonomous manner. These findings demonstrate the reliance of motoneurons on more Smn, thereby adding a novel piece of evidence for their increased vulnerability under SMA conditions.

Read online: Scientific Reports

Multistep nucleation of nanocrystals in aqueous solution

N. Duane Loh, Soumyo Sen, Michel Bosman, Shu Fen Tan, Jun Zhong, Christian A. Nijhuis, Petr Král, Paul Matsudaira & Utkur Mirsaidov

Nature Chemistry 9, 77–82 (2017) doi:10.1038/nchem.2618
Received 08 May 2016 Accepted 18 August 2016 Published online 03 October 2016

The nucleation and growth of solids from solutions impacts many natural processes and is fundamental to applications in materials engineering and medicine. For a crystalline solid, the nucleus is a nanoscale cluster of ordered atoms that forms through mechanisms still poorly understood. In particular, it is unclear whether a nucleus forms spontaneously from solution via a single- or multiple-step process. Here, using in situ electron microscopy, we show how gold and silver nanocrystals nucleate from supersaturated aqueous solutions in three distinct steps: spinodal decomposition into solute-rich and solute-poor liquid phases, nucleation of amorphous nanoclusters within the metal-rich liquid phase, followed by crystallization of these amorphous clusters. Our ab initio calculations on gold nucleation suggest that these steps might be associated with strong gold–gold atom coupling and water-mediated metastable gold complexes. The understanding of intermediate steps in nuclei formation has important implications for the formation and growth of both crystalline and amorphous materials.

Read online: Nature Chemistry.