CiteULike: neils's review

Protein-Protein Interactions in the Membrane: Sequence, Structural, and Biological Motifs

David Moore — 2008-07-10T03:35:58-00:00

Structure, Vol. 16, No. 7. (9 July 2008), pp. 991-1001.

Summary Single-span transmembrane (TM) helices have structural and functional roles well beyond serving as mere anchors to tether water-soluble domains in the vicinity of the membrane. They frequently direct the assembly of protein complexes and mediate signal transduction in ways analogous to small modular domains in water-soluble proteins. This review highlights different sequence and structural motifs that direct TM assembly and discusses their roles in diverse biological processes. We believe that TM interactions are potential therapeutic targets, as evidenced by natural proteins that modulate other TM interactions and recent developments in the design of TM-targeting peptides.

Food Idiosyncrasies: Beetroot and Asparagus

SC Mitchell — 2008-07-06T04:07:37-00:00

Drug Metab Dispos, Vol. 29, No. 4. (1 April 2001), pp. 539-543.

Anecdotal observations scattered throughout the literature have often provided clues to underlying variations in humans' ability to handle dietary chemicals. Beetroot, the red root of the garden beet used extensively as a food source, is known to produce red urine in some people following its ingestion, whereas others appear to be able to eat the vegetable with impunity. Asparagus, a vegetable whose young shoots have been eaten as a delicacy since the times of the Roman Empire, has been associated with the production of a malodorous urine smelling like rotten cabbage. Those who produce this odor assume that everyone does, and those who do not produce it have no idea of its potential olfactory consequences. These two examples, where the population appears divided in its ability to process food products or more precisely the chemicals contained within them, are reviewed in detail in this article.

Life Sciences and the web: a new era for collaboration

Jonathan Sagotsky — 2008-07-03T09:46:41-00:00

Mol Syst Biol, Vol. 4 (1 July 2008)

What makes pathogens pathogenic

Garth Ehrlich — 2008-06-25T00:15:15-00:00

Genome Biology, Vol. 9, No. 6. (2008)

Metazoans contain multiple complex microbial ecosystems in which the balance between host and microbe can be tipped from commensalism to pathogenicity. This transition is likely to depend both on the prevailing environmental conditions and on specific gene-gene interactions placed within the context of the entire ecosystem.

Sweet to the extreme: protein glycosylation in Archaea

Yurist-Doutsch — 2008-05-14T12:24:02-00:00

Molecular Microbiology, Vol. 68, No. 5. (June 2008), pp. 1079-1084.

Evolution and dynamics of protein interactions and networks

Emmanuel Levy — 2008-05-06T12:10:11-00:00

Current Opinion in Structural Biology, Vol. In Press, Corrected Proof

The central role of protein-protein interactions (PPIs) in biology has stimulated colossal efforts to identify thousands of them in several organisms. The resulting PPI maps are commonly represented as graphs, where nodes denote proteins and edges represent physical interactions. However, the methods used to generate PPI data on a large scale do not readily allow one to discriminate features such as interaction strength (affinity), type (protein-protein or protein-peptide interaction) or spatiotemporal existence (where and when the proteins are present and interact). Yet, in recent years, a number of studies have tackled these limitations by projecting additional information onto PPIs, revealing novel properties in terms of their evolution and dynamics. In this review we examine these properties both at the binary interaction level and at the network level. We suggest that the diverse and sometimes contradictory results described by different research groups are mostly due to incomplete data coverage and limited data types. Finally, we discuss recently developed methods that will improve this picture in the future.

Pathogenic archaea: do they exist?

R Cavicchioli — 2008-05-11T09:24:51-00:00

BioEssays : news and reviews in molecular, cellular and developmental biology, Vol. 25, No. 11. (November 2003), pp. 1119-1128.

Archaea are microorganisms that are distinct from bacteria and eukaryotes. They are prevalent in extreme environments, and yet found in most ecosystems. They are a natural component of the microbiota of most, if not all, humans and other animals. Despite their ubiquity and close association with humans, animals and plants, no pathogenic archaea have been identified. Because no archaeal pathogens have yet been identified, there is a general assumption that archaeal pathogens do not exist. This review examines whether this is a good assumption by investigating the potential for archaea to be or become pathogens. This is achieved by addressing: the diversity of archaea versus known pathogens, opportunities for archaea to demonstrate pathogenicity and be detected as pathogens, reports linking archaea with disease, and immune responses to archaea. In addition, molecular and genomic data are examined for the presence of systems utilised in pathogenesis. The view of this report is that, although archaea can presently be described as non-pathogenic, they have the potential to be (discovered as) pathogens. The present optimistic view that there are no archaeal pathogens is tainted by a severe lack of relevant knowledge, which may have important consequences in the future.

Calculation of protein-ligand binding affinities.

MK Gilson — 2008-01-23T22:59:03-00:00

Annu Rev Biophys Biomol Struct, Vol. 36 (2007), pp. 21-42.

Accurate methods of computing the affinity of a small molecule with a protein are needed to speed the discovery of new medications and biological probes. This paper reviews physics-based models of binding, beginning with a summary of the changes in potential energy, solvation energy, and configurational entropy that influence affinity, and a theoretical overview to frame the discussion of specific computational approaches. Important advances are reported in modeling protein-ligand energetics, such as the incorporation of electronic polarization and the use of quantum mechanical methods. Recent calculations suggest that changes in configurational entropy strongly oppose binding and must be included if accurate affinities are to be obtained. The linear interaction energy (LIE) and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methods are analyzed, as are free energy pathway methods, which show promise and may be ready for more extensive testing. Ultimately, major improvements in modeling accuracy will likely require advances on multiple fronts, as well as continued validation against experiment.

Advances in the Analysis of Protein Phosphorylation

Alberto Paradela — 2008-03-10T02:26:57-00:00

J. Proteome Res. (8 March 2008)

Abstract: Phosphorylation is one of the most relevant and ubiquitous post-translational modifications. Despite its relevance, the analysis of protein phosphorylation has been revealed as one of the most challenging tasks due to its highly dynamic nature and low stoichiometry. However, the development and introduction of new analytical methods are modifying rapidly and substantially this field. Especially important has been the introduction of more sensitive and specific methods for phosphoprotein and phosphopeptide purification as well as the use of more sensitive and accurate MS-based analytical methods. The integration of both approaches has enabled large-scale phosphoproteome studies to be performed, an unimaginable task few years ago. Additionally, methods originally developed for differential proteomics have been adapted making the study of the highly dynamic nature of protein phosphorylation feasible. This review aims at offering an overview on the most frequently used methods in phosphoprotein and phosphopeptide enrichment as well as on the most recent MS-based analysis strategies. Current strategies for quantitative phosphoproteomics and the study of the dynamics of protein phosphorylation are highlighted.

Extensible open source content management systems and frameworks: a solution for many needs of a bioinformatics group

Sean Mooney — 2008-02-23T01:31:26-00:00

Brief Bioinform, Vol. 9, No. 1. (1 January 2008), pp. 69-74.

A common challenge for bioinformaticians, in either academic or industry laboratory environments, is providing informatic solutions via the Internet or through a web browser. Recently, the open source community began developing tools for building and maintaining web applications for many disciplines. These content management systems (CMS) provide many of the basic needs of an informatics group, whether in a small company, a group within a larger organisation or an academic laboratory. These tools aid in managing software development, website development, document development, course development, datasets, collaborations and customers. Since many of these tools are extensible, they can be developed to support other research-specific activities, such as handling large biomedical datasets or deploying bioanalytic tools. In this review of open source website management tools, the basic features of content management systems are discussed along with commonly used open source software. Additionally, some examples of their use in biomedical research are given. 10.1093/bib/bbm057

Classical nuclear localization signals: definition, function, and interaction with importin alpha.

A Lange — 2008-02-21T01:54:12-00:00

J Biol Chem, Vol. 282, No. 8. (23 February 2007), pp. 5101-5105.

The best understood system for the transport of macromolecules between the cytoplasm and the nucleus is the classical nuclear import pathway. In this pathway, a protein containing a classical basic nuclear localization signal (NLS) is imported by a heterodimeric import receptor consisting of the beta-karyopherin importin beta, which mediates interactions with the nuclear pore complex, and the adaptor protein importin alpha, which directly binds the classical NLS. Here we review recent studies that have advanced our understanding of this pathway and also take a bioinformatics approach to analyze the likely prevalence of this system in vivo. Finally, we describe how a predicted NLS within a protein of interest can be confirmed experimentally to be functionally important.

No evidence of a Neanderthal contribution to modern human diversity

Jason Hodgson — 2008-02-18T22:19:56-00:00

Genome Biology, Vol. 9, No. 2. (2008)

The relationship between Neanderthals and modern humans is contentious, but recent advances in Neanderthal genomics have shed new light on their evolutionary history. Here we review the available evidence and find no indication of any Neanderthal contribution to modern genetic diversity.

Phosphoinositide 3-kinase: the protein kinase that time forgot.

LC Foukas — 2008-01-08T09:51:11-00:00

Biochem Soc Trans, Vol. 32, No. Pt 2. (April 2004), pp. 330-331.

Class I phosphoinositide 3-kinases were originally characterized as lipid kinases, although more than 10 years ago they were also found to phosphorylate protein serine residues. However, while there is a vast amount of data on the function of this lipid kinase activity, relatively little is known about the function of the protein kinase activity. We discuss the evidence that suggests that the protein kinase activity of phosphoinositide 3-kinases mediates important signalling functions in cells.

When is a lipid kinase not a lipid kinase? When it is a protein kinase.

T Hunter — 2008-01-08T09:48:00-00:00

Cell, Vol. 83, No. 1. (6 October 1995), pp. 1-4.