2014N62

Inaba san (Nature v 508, 7495, 7497)

Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion

This paper discusses the mechanism using which the amoeba Entamoeba Histolytica kills the host cells. It has been established that the parasite uses toxins to kill the cells before ingesting it. But here the authors discover that the amoeba kills by ingesting distinct pieces of living human cells, resulting in intracellular calcium elevation and eventual cell death. This model is entirely opposite to that of the established models. Owing to its similarity with trogocytosis observed in immune cells, there might be a possible evolutionary consequence behind it.

Juno is the egg Izumo receptor and isessential for mammalian fertilization

The molecular basis of recognition of an egg by a sperm has remained a mystery to researchers. It is known that there are proteins called IZUMO on the surface of sperm cells which gets recognised at the egg. But up until now, the receptor molecule at the surface of the egg has boot been identified. In this paper, the authors discover a Folate Receptor (Folr4) on the surface of the mouse egg as the receptor for IZUMO.

Structure of the LH1-RC complex from Thermochromatium tepidum at 3.0_

This paper is the first report of the near atomic structure of the light harvesting core antennae (LH1) - reaction centre (RC) complex from a purple photosynthetic bacteria Thermochromatium tepidum. This structure helps us to enhance our understanding of the molecular mechanism of the energy transfer from LH1 to RC, and the ubiquinone shuttling.

ZHU san (Nature 7498, 7500)

Cystathionine gamma-lyase deficiency mediates neurodegeneration in Huntington's disease

The molecular mechanisms that regulates the neurotoxicity in case of Huntington's has not been entirely studied. In this paper the authors find that there is a decrease in transcriptional activation of cystathionine c-lyase by mHTT (mutated huntingtin gene) and they suggest that this might be the reason behind the neurological impairment. This finding suggests that supplementation using cysteine source such as N-acetlycysteine may be useful in treating the disease.

Structure of the human P2Y12 receptor in complex with an antithrombotic drug

P2Y12 is one of the 8 distinct P2YRs in humans. These G- protein coupled receptors are activated by extracellular nucleotides. Recently, AstraZenca introduced AZD1283 as a novel P2Y12 antagonist for arterial thrombosis therapy. In this paper, the authors solve the structure of a P2Y12 in complex with AZD1283 at a resolution of 2.6 A. The structure complements the previous biochemical and mutational studies done on this protein. It is also interesting to note that this structure has some interesting features in the helix 5, 7 and 6, distinct localisation and shape of the pocket of binding of AZD1283, thus sets it apart from other previously solved structures of this family of GPCRs.

Kojima san (Science [6173, 2/21], [6176, 3/14], [6183, 5/2])

Structural Insights into Ubiquinone Biosynthesis in Membranes

The crystal structure of the Ubiquinone Biosynthesis A enzyme has been solved in its apo and substrate binding state at 3.3A and 3.6A respectively. The comparison of the electron density maps of the apo and substrate bound state highlights the structural differences. The knowledge of this structural information forms the basis of the substrate recognition and catalysis. It is also known that mutations in this protein results in cardiovascular disease and Parkinson's in eukaryotes. Thus this structural information would help in the rational understanding of such lethal mutations.

Structures of Cas9 Endonucleases Reveal RNA-Mediated Conformational Activation

In type 2 CRISPR system the RNA guided endonuclease cas 9 recognises and cleaves the target dsDNA. The authors report the atomic structures of Cas9 from Streptococcus pyogenes and Actinomyces naeslundii. The structures pointed towards a conserved structural core in the nuclease domain whereas the diversity in the structures in PAM recognition motifs may be attributed to the difference in guide RNA and PAM preferences. The apo structure is catalytically inactive and the authors speculate a role for the guide RNA in activating the DNA binding ability of the cas9.

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