| RESEARCH HIGHLIGHTS |
Previous research has linked NKTCL
with infection with Epstein-Barr virus, which Khor says is usually relatively harmless in the body. It is still not known why Epstein-Barr could trigger NKTCL, although it has also
been linked to the development of another type of nasal cancer. “Normally our immune system is good,
strong, and is able to control the virus well. How- ever, sometimes, when the immune system is weaker, the virus is not so well controlled. In that
light, perhaps the virus could have malignant transformative potential,” Khor says.
1. Li, Z., Xia, Y., Feng, L., Chen, J., Li, H. et al. Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study. The Lancet Oncology 17, 1240–1247 (2016).
Structural biology:
X-RAY CRYSTAL STRUCTURE OF A HUMAN PROTEIN COMPLEX
SOLVING THE 3D STRUCTURE OF A NEWLY OBSERVED PROTEIN COMPLEX IN MAMMALIAN CELLS PAVES THE WAY FOR INTERESTING APPLICATIONS
The first three-dimensional (3D) structure of a human protein complex within intact mammalian cells has been obtained directly by A*STAR scientists1. It could provide new opportunities in structural biology, in developing cellular sensors and in validating anti-cancer drugs that target a specific protein. The complex generates a highly ordered
honeycomb shape made of two proteins: PAK4 (p21-activated kinase 4) and its newly discovered inhibitor Inka1. PAK4 is essential for several cellular processes occurring in the junctions between cells, and when malfunctioning, plays a role in cancer metastasis. “We discovered that Inka1 is the natural
inhibitor of PAK4, and we observed by chance that when mammalian cells are engineered to make both these proteins, PAK4 spontaneously forms long crystals,” reveals Ed Manser, from the A*STAR Institute of Molecular Biology and Cell Biology. The group were the first to discover the PAK kinases.
www.astar-research.com Creating highly ordered arrangements of
proteins, known as protein ‘crystals’, is the first step to determine their 3D structure through X-ray analysis. Since it is very rare for these crystals to form inside a cell, all protein 3D structures obtained so far have been crystallized artificially, from highly pure and homogeneous protein samples. In this study, however, the atomic structure can be determined without removing the crystals from the cells. Teaming up with Robert Robinson's
group, and using an X-ray microbeam to shoot at these tiny intracellular crystals, the scientists were able to achieve a high structural resolution of 0.295 nanometers — comparable to the one obtained with PAK4 complexes crystallized outside of the cell. The research team also took advantage
of the organization of this crystal. The PAK4 forms a hexagonal frame, similar to wax cells in a honeycomb. This hexagonal scaffolding has internal channels that can host other proteins. In the first instance, the
The organization of proteins PAK4 (red and blue) and Inka1 (light blue) as determined from crystals formed inside cells.
A*STAR RESEARCH 43
research team fused Inka1 with a well-known fluorescent protein called GFP, allowing them to follow crystal growth with much
© 2016 A*STAR Institute of Molecular and Cell Biology
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