Archive for November, 2011

HOT: Intrinsically disordered GTPase from Bacillus pasteurii

In this paper Barbara Zambelli and colleagues discuss the first known intrinsically disordered enzyme which exhibits activity in its disordered state. This protein, BpUreG, from Bacillus pasteurii exists in three different forms depending on the temperature and concentration of denaturant used.

Researcher insight:
Intrinsic disorder is well known to play a role in some key regulative functions in proteins, while enzymatic activity is generally associated with overall protein rigidity, and only few cases of artificial intrinsically disordered enzymes have been reported so far. The present study provides insights into the folding landscape sampled by BpUreG, the first discovered native intrinsically disordered enzyme, known to be active in its unstructured state. A combination of spectroscopic and calorimetric techniques revealed that this enzyme exists as an ensemble of uncooperatively interconverting conformational states, whose degree of structure depends on temperature and denaturant concentration.

- Barbara Zambelli

Insights in the (un)structural organization of Bacillus pasteurii UreG, an intrinsically disordered GTPase enzyme
Barbara Zambelli, Nunilo Cremades, Paolo Neyroz, Paola Turano, Vladimir N. Uversky and Stefano Ciurli
Mol. BioSyst., 2012, Advance Article
DOI: 10.1039/C1MB05227F, Paper

This article is part of our themed issue on intrinsically disordered proteins and is currently free to access for 4 weeks. Don’t forget to check all the other hot articles in this issue!

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HOT: Intrinsic disorder in the androgen receptor – identification, characterization and drugability

This review article by Iain J McEwan focusses on the androgen receptor (AR) which regulates gene expression in response to testosterone and dihydrotestosterone. The ‘collapsed disordered’ structure of the N-terminal portion of the molecule is discussed in relation to its role in protein-protein interactions and as a potential target site for drug action.

Researcher insight:
The structurally plastic N-terminal domain (NTD) of steroid receptors is important for both receptor function and allosteric regulation; and adopts a helical conformation upon receptor binding to DNA and co-regulatory proteins. In an exciting recent development the function of this region of the androgen receptor was found to be directly inhibited by a small molecule, which switched off receptor activity in a wide range of functional assays.

- Iain J. McEwan

Intrinsic disorder in the androgen receptor: identification, characterisation and drugability
Iain J. McEwan
Mol. BioSyst., 2012, Advance Article
DOI: 10.1039/C1MB05249G, Review

This article is part of our themed issue on intrinsically disordered proteins and is currently free to access for 4 weeks. Don’t forget to check all the other hot articles in this issue!

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Top ten most accessed articles in October

This month sees the following articles in Molecular BioSystems that are in the top ten most accessed:

Structural analysis of intrinsically disordered proteins by small-angle X-ray scattering
Pau Bernadó and Dmitri I. Svergun
Mol. BioSyst., 2012, Advance Article
DOI: 10.1039/C1MB05275F

Characterization of ubiquitination dependent dynamics in growth factor receptor signaling by quantitative proteomics
Vyacheslav Akimov, Kristoffer T. G. Rigbolt, Mogens M. Nielsen and Blagoy Blagoev
Mol. BioSyst., 2011, 7, 3223-3233
DOI: 10.1039/C1MB05185G

Comprehensive miRNome and in silico analyses identify the Wnt signaling pathway to be altered in the diabetic liver
Kirandeep Kaur, Amit K. Pandey, Swayamprakash Srivastava, Arvind K. Srivastava and Malabika Datta
Mol. BioSyst., 2011, 7, 3234-3244
DOI: 10.1039/C1MB05041A

Large-scale network models of IL-1 and IL-6 signalling and their hepatocellular specification
Anke Ryll, Regina Samaga, Fred Schaper, Leonidas G. Alexopoulos and Steffen Klamt
Mol. BioSyst., 2011, 7, 3253-3270
DOI: 10.1039/C1MB05261F

The diversity of protein turnover and abundance under nitrogen-limited steady-state conditions in Saccharomyces cerevisiae
Andreas O. Helbig, Pascale Daran-Lapujade, Antonius J. A. van Maris, Erik A. F. de Hulster, Dick de Ridder, Jack T. Pronk, Albert J. R. Heck and Monique Slijper
Mol. BioSyst., 2011, 7, 3316-3326
DOI: 10.1039/C1MB05250K

Understanding the structural ensembles of a highly extended disordered protein
Gary W. Daughdrill, Stepan Kashtanov, Amber Stancik, Shannon E. Hill, Gregory Helms, Martin Muschol, Véronique Receveur-Bréchot and F. Marty Ytreberg
Mol. BioSyst., 2012, Advance Article
DOI: 10.1039/C1MB05243H

Visualization of phosphatase activity in living cells with a FRET-based calcineurin activity sensor
Robert H. Newman and Jin Zhang
Mol. BioSyst., 2008, 4, 496-501
DOI: 10.1039/B720034J

Global signatures of protein and mRNA expression levels
Raquel de Sousa Abreu, Luiz O. Penalva, Edward M. Marcotte and Christine Vogel
Mol. BioSyst., 2009, 5, 1512-1526
DOI: 10.1039/B908315D

Molecular mechanisms linking diabetes mellitus and Alzheimer disease: beta-amyloid peptide, insulin signaling, and neuronal function
Shuko Takeda, Naoyuki Sato, Hiromi Rakugi and Ryuichi Morishita
Mol. BioSyst., 2011, 7, 1822-1827
DOI: 10.1039/C0MB00302F

Bromodomain-peptide displacement assays for interactome mapping and inhibitor discovery
Martin Philpott, Jing Yang, Tony Tumber, Oleg Fedorov, Sagar Uttarkar, Panagis Filippakopoulos, Sarah Picaud, Tracy Keates, Ildiko Felletar, Alessio Ciulli, Stefan Knapp and Tom D. Heightman
Mol. BioSyst., 2011, 7, 2899-2908
DOI: 10.1039/C1MB05099K

Why not take a look at the articles today and blog your thoughts and comments below.

Fancy submitting an article to Molecular BioSystems? Then why not submit to us today or alternatively email us your suggestions.

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HOT: new insights into alpha-synuclein permeabilisation mechanisms in Parkinson’s disease

This hot article from Martin Stöckl et al. provides new insight into the toxic role of α-synuclein – a protein associated with the development and progression of Parkinson’s disease.

α-synuclein oligomers are thought to cause neuronal death by permeabilising the cellular membrane.  Here Stöckl et al. show that more than one mechanism may be active to cause this – oligomers could form pores allowing the passage of small molecules into the neurons by insertion into membranes or their interaction with the membrane may disrupt lipid packing, resulting in membrane defects.  They also show that α-synuclein increases the flip-flop rate of the lipid membranes.

Researcher insight:
Oligomeric forms of α-synuclein are thought to impair cellular membrane integrity in the development of Parkinson’s Disease (PD). This study demonstrates that oligomeric α-synuclein not only permeabilizes lipid bilayers, but also causes an enhanced lipid flip-flop between the outer and inner leaflets, revealing a novel mechanism which could contribute to membrane destabilization and eventually neuronal death in PD.

-Vinod Subramaniam

Kinetic measurements give new insights into lipid membrane permeabilization by α-synuclein oligomers
Martin Stöckl, Mireille M. A. E. Claessens and Vinod Subramaniam
DOI: 10.1039/C1MB05293D

This article is part of our themed issue on intrinsically disordered proteins and is currently free to access for 4 weeks. Don’t forget to check all the other hot articles in this issue!

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HOT: exploring mechanisms of long distance cell signal travel

Ruth Nussinov, NCI-Frederick, discusses the possible mechanisms that support long-range signalling in cells in this hot Opinion article.

She proposes that three key properties have evolved to enable signals to travel rapidly over comparatively vast cellular distances: 1) modular organisation according to protein function, 2) sequences are ‘pre-encoded’ to facilitate signalling and 3) intrinsically disordered proteins enable fast signal transmission through dense packing.

Researcher insight:

This paper proposes that conformational disorder can help faster propagation of signals across the cell. When disordered proteins bind, their interface is tightly packed. Dense packing facilitates efficient transmission of the allosteric energy wave, which leads to fast cellular response to external stimuli.

-Ruth Nussinov

How do dynamic cellular signals travel long distances?
Ruth Nussinov
DOI: 10.1039/C1MB05205E

This article is part of our themed issue on intrinsically disordered proteins and is currently free to access for 4 weeks. Don’t forget to check all the other hot articles in this issue!

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Challenges in Organic Chemistry and Chemical Biology symposium

The first of the International Symposia on Advancing the Chemical Sciences (ISACS) series next year is to be Challenges in Organic Chemistry and Chemical Biology (ISACS7) on 12 – 15 June at the University of Edinburgh, UK.

See the excellent list of confirmed speakers and details of the abstract submission process here.

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HOT: Intrinsically disordered proteins as molecular shields to prevent protein aggregation

Late embryogenesis abundant (LEA) proteins are intrinsically disordered proteins (IDPs) with a role in limiting the aggregation of proteins in cells that are exposed to water loss.  In this hot article Sohini Chakrabortee et al. show that the LEA IDPs act differently from well-structured molecular chaperone proteins by physically preventing aggregation, and have coined the term molecular shields to describe them.

Researcher insight:
Some intrinsically disordered proteins associated with desiccation tolerance have a novel function: they behave as molecular shields, reducing the rate of aggregation of other, aggregation-prone proteins. In this article, molecular shields are shown to be distinct from molecular chaperones, instead resembling polymeric stabilisers of colloidal suspensions and implicating a role in stabilisation of the cell cytoplasm during water stress.

-Alan Tunnacliffe

Intrinsically disordered proteins as molecular shields
Sohini Chakrabortee, Rashmi Tripathi, Matthew Watson, Gabriele S. Kaminski Schierle, Davy P. Kurniawan, Clemens F. Kaminski, Michael J. Wise and Alan Tunnacliffe
DOI: 10.1039/C1MB05263B

This article is part of our themed issue on intrinsically disordered proteins and is currently free to access for 4 weeks. Don’t forget to check all the other hot articles in this issue!

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Molecular BioSystems authors win $10,000 award for innovation in human health research

Authors of a recent Molecular BioSystems paper on a high-throughput epifluorescence microscopy method for the discovery of inhibitors of biofilm formation in cholera have won the Deloitte QB3 Award for Innovation.  The award is given to ‘the student, postdoc, or staff scientist (or team) whose research has been deemed to have the greatest capacity to advance human health’ – with a reward of $10,000.  The winning team from University of California Santa Cruz consist of Kelly Peach, Nicholas Shikuma, and Walter Bray.

Roger Linington, senior author on the paper, nominated the team for the award, “I feel that this awards highlights some of the high quality interdisciplinary research being fostered by the UCSC Chemical Screening Center. It is a testament to the value of cross-specialization projects such as this that the results were chosen for this award by the qb3 community. Fitnat Yildiz, Scott Lokey and I are certainly delighted that our team were the eventual winners of this award, and look forward to extending these results to broader screening and target identification projects.”

Congratulations to all involved, we’ve made the article free to access* for the next four weeks, so why not take a look at this award-winning piece of research:

An image-based 384-well high-throughput screening method for the discovery of biofilm inhibitors in Vibrio cholerae
Kelly C. Peach, Walter M. Bray, Nicholas J. Shikuma, Nadine C. Gassner, R. Scott Lokey, Fitnat H. Yildiz and Roger G. Linington, Mol. BioSyst., 2011, 7, 1176-1184
DOI: 10.1039/C0MB00276C

*Following a simple registration for individual users
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On the cover: new lung cancer miRNAs identified through next generation sequencing

The hot article on the cover of this month’s issue is from Andreas Keller and Christina Backes et al. whose artwork shows their discovery of novel microRNAs in peripheral blood of lung cancer patients.  Using high-throughput SOLiD transcriptome sequencing they identified 76 previously unknown miRNAs and 41 novel mature forms of known precursors, which may potentially be used as biomarkers for the disease.

Download the article to read more about this interesting piece of research, which is part of the larger ‘‘Whole Disease miRNome’’ project which aims to improve our understanding of the human miRNome in a wide range of human diseases.

Next-generation sequencing identifies novel microRNAs in peripheral blood of lung cancer patients
Andreas Keller, Christina Backes, Petra Leidinger, Nathalie Kefer, Valesca Boisguerin, Catalin Barbacioru, Britta Vogel, Mark Matzas, Hanno Huwer, Hugo A. Katus, Cord Stähler, Benjamin Meder and Eckart Meese
DOI: 10.1039/C1MB05353A

View the rest of Issue 12, including hot articles on predicting antibody complementarity and how fluorescent labelling agents change binding profiles of glycan-binding proteins.

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HOT articles in Issue 12 – predicting antibody complementarity, labelling affects GBPs & new lung cancer miRNAs found

The complementarity determining regions (CDRs) in antibodies define the majority of their antigen binding functionality, and as such have been well studied and classified.  Here it is shown that CDR structure can be predicted in the same way as standard loop structures using FREAD, a successful database loop prediction technique. FREAD is able to predict CDR loops accurately and without classification, to account for structural changes of CDRs on binding the antigens.

Predicting antibody complementarity determining region structures without classification
Yoonjoo Choi and Charlotte M. Deane
DOI: 10.1039/C1MB05223C


Interactions of glycan-binding proteins (GBPs) with glycans are essential in cell adhesion, bacterial/viral infection, and cellular signalling pathways, but typical methods to measure them experimentally such as ex situ fluorescence-based assays can be inaccurate.  This study addresses some of the pitfalls associated with ex situ fluorescence assays such as alterations in the affinity of glycans for the GBPs.

Fluorescent labeling agents change binding profiles of glycan-binding proteins
Yiyan Fei, Yung-Shin Sun, Yanhong Li, Kam Lau, Hai Yu, Harshal A. Chokhawala, Shengshu Huang, James P. Landry, Xi Chen and Xiangdong Zhu
DOI: 10.1039/C1MB05332A


microRNAs have the potential to act as biomarkers for various disease,s including cancer.  This hot article reports the detection of 76 previously unknown miRNAs and 41 novel mature forms of known precursors in peripheral blood of lung cancer patients using high-throughput SOLiD transcriptome sequencing.

Next-generation sequencing identifies novel microRNAs in peripheral blood of lung cancer patients
Andreas Keller, Christina Backes, Petra Leidinger, Nathalie Kefer, Valesca Boisguerin, Catalin Barbacioru, Britta Vogel, Mark Matzas, Hanno Huwer, Hugo A. Katus, Cord Stähler, Benjamin Meder and Eckart Meese
DOI: 10.1039/C1MB05353A

As with all our hot articles, these are free to access for 4 weeks.* You can also view the rest of Issue 12 online here

* following a simple registration for individual users

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