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Copenhagen, Denmark

Malik L.,Copenhagen University | Nygaard J.,Copenhagen University | Nygaard J.,Lund University | Christensen N.J.,Copenhagen University | And 4 more authors.
Journal of Peptide Science | Year: 2013

α-Helical coiled coil structures, which are noncovalently associated heptad repeat peptide sequences, are ubiquitous in nature. Similar amphipathic repeat sequences have also been found in helix-containing proteins and have played a central role in de novo design of proteins. In addition, they are promising tools for the construction of nanomaterials. Small-angle X-ray scattering (SAXS) has emerged as a new biophysical technique for elucidation of protein topology. Here, we describe a systematic study of the self-assembly of a small ensemble of coiled coil sequences using SAXS and analytical ultracentrifugation (AUC), which was correlated with molecular dynamics simulations. Our results show that even minor sequence changes have an effect on the folding topology and the self-assembly and that these differences can be observed by a combination of AUC, SAXS, and circular dichroism spectroscopy. A small difference in these methods was observed, as SAXS for one peptide and revealed the presence of a population of longer aggregates, which was not observed by AUC. © 2013 European Peptide Society and John Wiley & Sons, Ltd.

The logo of AstraZeneca is seen on a medication package in a pharmacy in London April 28, 2014. REUTERS/Stefan Wermuth More LONDON (Reuters) - AstraZeneca is diving into the world of proteins secreted by cells - collectively known as the secretome - in the hunt for new drugs and better "cell factories" for making biotech medicines. The so-called secretome accounts for around one third of human proteins and the idea of mapping them all follows the decoding of the human genome in 2000, since when there has been a surge in scientific buzzwords ending in "ome". The secretome is one of the newest as scientists only unraveled the full array of proteins involved at the start of this year. As a result, its potential as a resource for pharmaceutical research remains largely unexplored. AstraZeneca hopes to get in on the ground floor of this opportunity through a three-year collaboration with the newly established Wallenberg Center for Protein Research in Sweden. The new center is being funded primarily by the Wallenberg family, which also owns Investor, the third largest shareholder in AstraZeneca. The Wallenberg Foundation is providing a $37 million grant over eight years for the center, while the Anglo-Swedish drugmaker will contribute $1.2 million a year for three years. In addition to hunting new drug targets for diseases ranging from heart disease to cancer, AstraZeneca said in a statement on Friday that its experts would also be looking at protein secretion processes that could improve medicine manufacturing. Currently, the drugs industry relies on a limited number of cell types - notably Chinese hamster ovary cells - to make biotech drugs in large fermentation vats. In future, there may be the potential to tap other kinds of cells that are better suited for large-scale production.

Dinkel H.,SCB Unit | Chica C.,SCB Unit | Chica C.,French Atomic Energy Commission | Via A.,University of Rome La Sapienza | And 5 more authors.
Nucleic Acids Research | Year: 2011

The Phospho.ELM resource (http://phospho.elm.eu.org) is a relational database designed to store in vivo and in vitro phosphorylation data extracted from the scientific literature and phosphoproteomicanalyses. The resource has been actively developed for more than 7 years and currently comprises 42 574 serine, threonine and tyrosine non-redundant phosphorylation sites. Several new features have been implemented, such as structural disorder/ order and accessibility information and a conservation score. Additionally, the conservation of the phosphosites can now be visualized directly on the multiple sequence alignment used for the score calculation. Finally, special emphasis has been put on linking to external resources such as interaction networks and other databases. © The Author(s) 2010.

Cepeda D.,Karolinska Institutet | Ng H.-F.,Karolinska Institutet | Sharifi H.R.,Karolinska Institutet | Mahmoudi S.,Karolinska Institutet | And 26 more authors.
EMBO Molecular Medicine | Year: 2013

SCF (Skp1/Cul1/F-box) ubiquitin ligases act as master regulators of cellular homeostasis by targeting key proteins for ubiquitylation. Here, we identified a hitherto uncharacterized F-box protein, FBXO28 that controls MYC-dependent transcription by non-proteolytic ubiquitylation. SCFFBXO28 activity and stability are regulated during the cell cycle by CDK1/2-mediated phosphorylation of FBXO28, which is required for its efficient ubiquitylation of MYC and downsteam enhancement of the MYC pathway. Depletion of FBXO28 or overexpression of an F-box mutant unable to support MYC ubiquitylation results in an impairment of MYC-driven transcription, transformation and tumourigenesis. Finally, in human breast cancer, high FBXO28 expression and phosphorylation are strong and independent predictors of poor outcome. In conclusion, our data suggest that SCFFBXO28 plays an important role in transmitting CDK activity to MYC function during the cell cycle, emphasizing the CDK-FBXO28-MYC axis as a potential molecular drug target in MYC-driven cancers, including breast cancer. FBXO28 is identified as part of a SCF complex acting as a regulator of tumor cell proliferation and an important modifier of MYC function. FBXO28 may be a new prognostic factor in breast cancer and a new potential drug target in MYC- driven tumors. © 2013 The Authors.

Jimenez R.C.,EMBL EBI | Albar J.P.,National Center for Biotecnology | Bhak J.,Theragen Bio Institute | Blatter M.-C.,Swiss Institute of Bioinformatics | And 31 more authors.
Bioinformatics | Year: 2013

We present iAnn, an open source community-driven platform for dissemination of life science events, such as courses, conferences and workshops. iAnn allows automatic visualisation and integration of customised event reports. A central repository lies at the core of the platform: curators add submitted events, and these are subsequently accessed via web services. Thus, once an iAnn widget is incorporated into a website, it permanently shows timely relevant information as if it were native to the remote site. At the same time, announcements submitted to the repository are automatically disseminated to all portals that query the system. To facilitate the visualization of announcements, iAnn provides powerful filtering options and views, integrated in Google Maps and Google Calendar. All iAnn widgets are freely available.Availability: http://iann.pro/ iannviewerContact: © 2013 The Author 2013. Published by Oxford University Press.

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