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Lucas A.T.,Virginia Bioinformatics Institute | Lucas A.T.,United Domains | Fu X.,Virginia Bioinformatics Institute | Liu J.,Virginia Bioinformatics Institute | And 5 more authors.
PLoS ONE | Year: 2014

The translationally-controlled tumor protein (TCTP) is a highly conserved, ubiquitously expressed, abundant protein that is broadly distributed among eukaryotes. Its biological function spans numerous cellular processes ranging from regulation of the cell cycle and microtubule stabilization to cell growth, transformation, and death processes. In this work, we propose a new function for TCTP as a "buffer protein" controlling cellular homeostasis. We demonstrate that binding of hemin to TCTP is mediated by a conserved His-containing motif (His76His77) followed by dimerization, an event that involves ligand-mediated conformational changes and that is necessary to trigger TCTP's cytokine-like activity. Mutation in both His residues to Ala prevents hemin from binding and abrogates oligomerization, suggesting that the ligand site localizes at the interface of the oligomer. Unlike heme, binding of Ca2+ ligand to TCTP does not alter its monomeric state; although, Ca2+ is able to destabilize an existing TCTP dimer created by hemin addition. In agreement with TCTP's proposed buffer function, ligand binding occurs at high concentration, allowing the "buffer" condition to be dissociated from TCTP's role as a component of signal transduction mechanisms. © 2014 Lucas et al.


Xiao S.,United Domains | Zhao X.,United Domains | Finkielstein C.V.,Virginia Bioinformatics Institute | Capelluto D.G.S.,United Domains
Journal of Peptide Science | Year: 2014

A procedure for obtaining isotopically labeled peptides, by combining affinity chromatography, urea-equilibrated gel filtration, and hydrophobic chromatography procedures, is presented using the Disabled-2 (Dab2) sulfatide-binding motif (SBM) as a proof of concept. The protocol is designed to isolate unstructured, membrane-binding, recombinant peptides that co-purify with bacterial proteins (e.g., chaperones). Dab2 SBM is overexpressed in bacteria as an isotopically labeled glutathione S-transferase (GST) fusion protein using minimal media containing [15N] ammonium chloride as the nitrogen source. The fusion protein is purified using glutathione beads, and Dab2 SBM is released from GST using a specific protease. It is then dried, resuspended in urea to release the bound bacterial protein, and subjected to urea-equilibrated gel filtration. Urea and buffer reagents are removed using an octadecyl column. The peptide is eluted with acetonitrile, dried, and stored at -80°C. Purification of Dab2 SBM can be accomplished in 6 days with a yield of ~2 mg/l of culture. The properties of Dab2 SBM can be studied in the presence of detergents using NMR spectroscopy. Although this method also allows for the purification of unlabeled peptides that co-purify with bacterial proteins, the procedure is more relevant to isotopically labeled peptides, thus alleviating the cost of peptide production. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.


United Domains | Entity website

Florian Huberverantwortet als CEO die Bereiche "Produkt" und "Technik" und sorgt mit seinem Team fr sichere, ausfallfreie und leicht zu bedienende Produkte


United Domains | Entity website

Florian Huberverantwortet als CEO die Bereiche "Produkt" und "Technik" und sorgt mit seinem Team fr sichere, ausfallfreie und leicht zu bedienende Produkte


United Domains | Entity website

Florian Huberverantwortet als CEO die Bereiche "Produkt" und "Technik" und sorgt mit seinem Team fr sichere, ausfallfreie und leicht zu bedienende Produkte


United Domains | Entity website

Florian Huberverantwortet als CEO die Bereiche "Produkt" und "Technik" und sorgt mit seinem Team fr sichere, ausfallfreie und leicht zu bedienende Produkte


United Domains | Entity website

Florian Huberverantwortet als CEO die Bereiche "Produkt" und "Technik" und sorgt mit seinem Team fr sichere, ausfallfreie und leicht zu bedienende Produkte


News Article | May 13, 2009
Site: gigaom.com

German magazine and digital publisher Hubert Burda Media is buying Lycos iQ, a question-and-answer community site that will be one of the final Lycos Europe assets to be offloaded. Despite failing to innovate to retain its once-mighty search engine status, the portal with the black dog logo had, over the last couple of years, routinely hailed the site – an imitation of Yahoo’s popular Answers counterpart – as one of its best homegrown projects. It currently has 750,000 users, but the UK version has gone off-line. A separate company from its US counterpart, Lycos Europe was unable to find a buyer last year so in December decided to liquidate instead. In asset-stripping, it’s managed to off-load its Jubii Denmark, United Domains and Shopping businesses, and even struck a deal to rescue Tripod from closure just days before a shutdown deadline. Next in the fire sale before the dog is put to sleep – the Pangora ecommerce network. Burda has extensive online operations under its Burda Digital Ventures wing, but the company, via Deutsche-Startups.de, says it wants to offer its mag editors’ knowledge to readers through Q&A. No price was disclosed.


Allen W.J.,Virginia Polytechnic Institute and State University | Capelluto D.G.S.,United Domains | Bevan D.R.,Virginia Polytechnic Institute and State University
Journal of Physical Chemistry B | Year: 2010

Fifty percent of all cancer cases result from mutations of the TP53 gene, which encodes the tumor suppressor p53, and it is hypothesized that the p53-mediated checkpoint pathway is compromised in most of the remaining cases. The p53 C-terminal domain (CTD) is an important site of p53 regulation but by nature is difficult to study, as it is intrinsically disordered. In this study, we performed molecular dynamics simulations on the p53 CTD and five known regulatory binding partners. We identified distinct trends in fluctuation within and around the p53 CTD binding site on each partner demonstrating a behavior that facilitates association. Further, we present evidence that the size of the hydrophobic pocket in each p53 CTD binding site governs the secondary structure of the p53 CTD when in the bound state. This information will be useful for predicting new binding partners for the p53 CTD, identifying interacting regions within other known partners, and discovering inhibitors that provide additional points of control over p53 activity. © 2010 American Chemical Society.

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