Structure of class C GPCR metabotropic glutamate receptor 5

Glutamate is the major excitatory neurotransmitter in the central nervous system. The metabotropic glutamate (mGlu) receptors can be divided into three groups on the basis of their sequence similarity. The mGlu5 is abundant through-out the cortex, hippocampus, striatum, and caudate nucleus, which involved in emotion, motivation and cognition.

Here, we reported that the structure was solved by molecular replacement with one copy of the receptor in the asymmetric unit. Structure analysis shows that mGlu receptors have an unusual structure comprising a large extracellular domain consisting of the VFT, which binds glutamate and a cysteine-rich domain (CRD). The most striking difference between mGlu5 and other receptor is the position ofTm5.

As mGlu5 is a promising therapeutic target and negative allosteric modulators (NAMs) which reduce mGlu5 receptor activation are undergoing clinical trials for the treatment of fragile X syndrome, depression, anxiety.

This work provides a detailed interpretation of the core domain of a class C GPCR, adding the extra-cellular domain structures. The mGlu5 receptor structure also increases our understanding of the mechanism of action of allosteric modulators for metabotropic receptors and will enable the design of modulators. There is a great promise in the treatment of severe neuropsychiatric disorders.

DNA methylation plays an important and crucial role in many biological processes, including repression of gene transcription, maintenance of gene imprinting and X-chromosome inactivation. In this study, we systematically profile the methylome of human early embryos from the zygotic stage through to post-implantation by whole-genome bisulphite sequencing.

The methylome of human embryos are similar to those of mouse embryos, but do have distinct features.A dramatic decrease in DNA methylation occurs between fertilization and the 2-cell stage, with the average level of methylation decreasing. This is contrary to previous observations in mice.

Next we analyzed the similarities and differences in DNA methylation between sperm and oocytes. The results show that the demethylation of the paternal genome is much faster than that of the maternal genome. When considering the relationship between DNA methylation and histone modifications, we use ChIP-Seq approach, and found that theH3K27me3 regions generally have low levels of DNA methylation in human ES cells and the ICM.

Our work provides understanding of the critical features of the methylome of human early embryos, as well as its functional relation to the regulation of gene expression and the repression of transposable elements.

Numerologist Warda is hooked on OG-L002 fishing, collecting. And lastly her encouragement comes from socializing along with her companions.