SV40, RNAi, XDR-TB, etc
Crystal Structure of the SV40 T-Antigen Origin Binding Domain in Complex with DNA
Summary: How DNA replicates is a critical question for understanding life. DNA replication remains difficult to investigate in eukaryotes, where it involves a complex, multi-protein apparatus which initiates replication at multiple poorly-defined DNA sequences. This process is far easier to study in viral systems, where the DNA sequences at the origin of replication are well-defined and only one or two proteins are required to initiate replication. In simian virus 40 (SV40), the large T-antigen protein (T-ag) is responsible for recognizing DNA sequences required to start replication, called the origin of replication. SV40 T-ag can also cause DNA to melt or unwind. We report here the crystal structure of the DNA-binding domain of SV40 T-ag on a DNA fragment derived from the viral origin of replication. The structure shows that although T-ag and its functionally analogous protein, papilloma virus E1, share no detectable sequence homology in this region, the two domains bind the DNA in similar ways. In both cases, DNA binding is thought to initiate assembly of a complex of the full-length proteins on DNA. Interestingly, SV40 T-ag DNA-binding domains do not interact with one another when bound to DNA. In addition to describing the molecular details of the DNA–protein interactions and the alterations in protein structure induced by DNA binding, we present a model describing the subsequent assembly events.
Meinke, G. et al. PLoS Biol 5(2): e23
Video of RNAi in action
Kudos to Biosingularity for pointing to this excellent YouTube video of RNAi:
XDR-TB in South Africa: No Time for Denial or Complacency
Some months ago, I recorded a podcast about extreme drug resistant tuberculosis (XDR-TB). Now a paper in PLoS Medicine argues that the situation is so serious that affected patients should be forcibly isolated to stop the disease spreading.
The South African outbreak of the multi drug-resistant XDR-TB has killed at least 74 people in the past few months. South Africa is one of the world’s fastest growing tourist destinations, home to millions of migrant labourers from neighbouring countries, and its ports and roads service several other African countries. Seroprevalence rates for HIV in South Africa, and in adjoining nations such as Lesotho and Swaziland, are very high. Cumulatively, these factors make for a potentially explosive international health crisis.
“All reasonable attempts must be made to accommodate the interests of infected patients in a sensitive and humane manner, although, if necessary, the government must adopt a more robust approach towards uncooperative patients with MDR-TB and XDR-TB, which might necessitate favouring the interests of the wider public over that of the patient. Although such an approach might interfere with the patient’s right to autonomy and will undoubtedly have human rights implications, such measures are reasonable and justifiable, and must be seen in a utilitarian perspective. Ultimately in such crises, the interests of public health must prevail over the rights of the individual.”
Singh JA,et al. 2007 XDR-TB in South Africa: No Time for Denial or Complacency. PLoS Med 4(1): e50
Sir Alec Jeffreys: Great Briton
Professor Sir Alec Jeffreys of the School of Biological Sciences at the University of Leicester has been chosen as the overall Greatest Briton 2006. Congratulation Alec, and warmly deserved, but aren’t you running out of space for all those trophies? ;-)
Microscopy in focus
Scientific American has an interesting article on Sidestepping microscopy’s limits: out-of-focus images made clear. Researchers have found a practical way to extract clear images from the parts of a sample illuminated by light above and below the focal plane. The new method may soon allow doctors to diagnose tumors without removing a piece of tissue from a patient.
