Bio Saga Blog - A Chronicle of Life Sciences & Informatics

Protein misfolding underlies many neurodegenerative diseases, including the transmissible spongiform encephalopathies (prion diseases). Although cells typically recognize and process misfolded proteins, prion proteins evade protective measures by forming stable, self-replicating aggregates. However, coexpression of dominant-negative prion mutants can overcome aggregate accumulation and disease progression through currently unknown pathways. Here we determine the mechanisms by which two mutants of the Saccharomyces cerevisiae Sup35 protein cure the [ PSI + ] prion. We show that both mutants incorporate into wild-type aggregates and alter their physical properties in different ways, diminishing either their assembly rate or their thermodynamic stability. Whereas wild-type aggregates are recalcitrant to cellular intervention, mixed aggregates are disassembled by the molecular chaperone Hsp104 . Thus, rather than simply blocking misfolding, dominant-negative prion mutants target multiple...

The glycoproteins (GP) of enveloped viruses facilitate entry into the host cell by interacting with specific cellular receptors. Despite extensive study, a cellular receptor for the deadly filoviruses Ebolavirus and Marburgvirus has yet to be identified and characterized. Here, we show that T-cell Ig and mucin domain 1 (TIM-1) binds to the receptor binding domain of the Zaire Ebola virus (EBOV) glycoprotein, and ectopic TIM-1 expression in poorly permissive cells enhances EBOV infection by 10- to 30-fold. Conversely, reduction of cell-surface expression of TIM-1 by RNAi decreased infection of highly permissive Vero cells. TIM-1 expression within the human body is broader than previously appreciated, with expression on mucosal epithelia from the trachea, cornea, and conjunctiva—tissues believed to be important during in vivo transmission of filoviruses. Recognition t...

Two-day national-level workshop on Protein Structural Analysis & Homology Modelling DATES: October 23-24, 2010 LOCALE: Department of Biotechnology and Bioinformatics,  Padmashree Dr. D. Y. Patil University Sector 15, CBD,  Belapur, Navi Mumbai-400614, India Janu Ganak and the Bioinformatics Community of the Department of Biotechnology and Bioinformatics, Padmashree Dr. D Y Patil  University, are pleased to inform you that a two day workshop on "PROTEIN STRUCTURAL ANALYSIS AND HOMOLOGY  MODELLING" is being organized.  This workshop is the second of a series of workshops that are aimed at  giving complete  hands-on experience in various tools and techniques  used  in the fields of life science and bioinformatics. This workshop is aimed at giving practical experience on the basic methods of visualization, analysis and modeling of protein structures using bioinformatics tools.  Both under-graduate...

The malaria parasite has waged a successful guerrilla war against the human immune system for eons, but a study in this week's Journal of Biological Chemistry has exposed one of the tricks malaria uses to hide from the immune proteins, which may aid in future drug development. Malaria parasites (plasmodia) are transmitted to people via infected mosquitoes. Once inside their human hosts the parasites first set up shop in liver cells, then move into red blood cells (RBCs) to replicate and wait for the next mosquito to help continue the cycle. After plasmodia infect a blood cell, they send out clusters of sticky proteins to the cell surface, enabling them to attach to blood vessels and escape destruction by the host's spleen while they replicate. This tactic can be especially problematic during pregnancy as malaria-infected RBCs congregate in the vessel-rich placenta (the source of food and oxygen for the growing fetus), creating health problems such as anemia, low birth-weight, f...

Dr. Ronald Collman talks about exciting new discoveries on HIV, the virus that has taken 25 million lives. Dr. Ronald Collman , professor of medicine in microbiology, virus/cell/molecular core director, Penn Center for AIDS Research, University of Pennsylvania.He describes the molecular structure, pathology, and with great insight, the incredible discoveries that might just help us conquer HIV. Listen to the Original audio source

Many of you involved in structure based drug discovery will know very well about the numerous problems and errors in the data found in the Protein Data Bank (PDB) especially concerning the ligand structures. There have been a lot of publications about such errors, e.g. in Jones et al. J Mol. Biol. (1997) 267 :727, and I heard various conference presentations about this topic too, e.g. by Gerard Kleywegt (University of Uppsala), titled “Protein crystallography: not as simple as ABC then?” at Bryn Mawr, Philadelphia (15-19 October 2007) eChemInfo meeting . The errors are often blamed on the low resolution of the structures involving large protein structures (often thousands of atoms). One would assume that the small molecule crystal structures of the Cambridge Structural Database ( CSD ) do not have such errors, since they have much higher resolution and dealing with small molecules. Let me correct that wrong assumption! Do you want to know more?

By studying the variety of chemical substances and their structures recorded in the CAS REGISTRY SM database, Chemical Abstracts Service (CAS) scientists have discovered that a limited number of molecular shapes are the frameworks for a disproportionately large percentage of reported substances. As shown in the CAS study , half of the known organic chemical substances can be described by just 143 shapes. The analysis, published in The Journal of Organic Chemistry , explains why certain molecular frameworks are more likely to be used in new compounds and may also help identify new regions of chemistry space ripe for exploration.

Leading scientists discuss DNA database at April 7-8 Meeting For a quarter century, GenBank has helped advance scientific discovery worldwide. Established by the National Institutes of Health (NIH) in 1982, the database of nucleic acid sequences is one of the key tools that scientists use to conduct biomedical and biologic research. Since its creation, GenBank has grown at an exponential rate, doubling in size every 18 months. In celebration of this vital resource and its contribution to science over the last 25 years, the National Center for Biotechnology Information, National Library of Medicine (NLM), NIH, is holding a two-day conference on GenBank. The conference will take place April 7-8, 2008 at the Natcher Conference Center on the main NIH campus in Bethesda, Maryland. For details on the meeting, see the conference Web site, at http://www.tech-res.com/GenBank25 . The conference is open to the public and also will be available via live and archived webcast; the April 7 proceedin...