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issn:1757-594
1.  Conformational changes in receptor tyrosine kinase signaling: an ErbB garden of delights 
F1000 biology reports  2009;1(72):1-4.
The ErbB family of receptor tyrosine kinases plays important roles in cell proliferation, differentiation, and apoptosis. Recent structural studies of these receptors have demonstrated dramatic conformational effects that are critical to their ligand binding and activation, and have shown that these receptors provide levels of control beyond the classic dimerization/activation mechanism. These results indicate that this class of receptors has evolved subtle regulatory mechanisms via genetic and protein structural changes to influence their effects on cell behaviors.
doi:10.3410/B1-72
PMCID: PMC2847299  PMID: 20357902
2.  Diversity of protein structures and difficulties in fold recognition: the curious case of protein G 
We examine the ability of current state-of-the-art methods in protein structure prediction to discriminate topologically distant folds encoded by highly similar (>90% sequence identity) designed proteins in blind protein structure prediction experiments. We detail the corresponding prognosis for the protein fold recognition field and highlight the features of the methodologies that successfully deciphered this folding riddle.
doi:10.3410/B1-69
PMCID: PMC2832337  PMID: 20209018
3.  The evolving story of orexin biology: the hits keep coming 
In the span of just 11 years since their discovery, the study of the orexins (hypocretins) has not only provided insight into the biology of sleep/wakefulness, but also demonstrated the importance of the development of new pharmacologic tools and genetic models with which to understand basic physiologic mechanisms and provide potential strategies for the treatment of human pathologies. Highlights from recently published novel approaches and findings are reviewed here.
doi:10.3410/B1-85
PMCID: PMC2886298  PMID: 20563314
4.  Setting the absolute threshold of vision 
The performance of sensory systems in many cases is limited by the physical nature of the stimulus. For vision, the quantal nature of light limits detection by dark-adapted observers; only now are we beginning to be aware of the subtleties in the biophysical mechanisms underlying this exquisite sensitivity.
doi:10.3410/B1-66
PMCID: PMC2873777  PMID: 20495680
5.  Do apicomplexan parasite-encoded proteins act as both ligands and receptors during host cell invasion? 
Apicomplexan parasites are responsible for a wide range of diseases in animals, including humans, in whom Plasmodium species cause the devastating disease malaria. Several recent discoveries now indicate that these intracellular parasites may use a conserved mechanism to infect their host cells by using parasite-encoded proteins as both parasite ligands and receptors anchored to the host cells.
doi:10.3410/B1-64
PMCID: PMC2832315  PMID: 20209017
6.  Vesicle coating and uncoating: controlling the formation of large COPII-coated carriers 
F1000 biology reports  2009;1:65-.
The basic mechanisms underlying the formation of coated vesicles are now defined in considerable detail. This article highlights recent developments in our understanding of the problem of exporting large macromolecular cargo such as procollagen from the endoplasmic reticulum and discusses the implications that this has for cell and tissue organisation and human disease.
PMCID: PMC2854804  PMID: 20401317
7.  Cryptococcus gattii outbreak expands into the Northwestern United States with fatal consequences 
In the past decade, the primary fungal pathogen Cryptococcus gattii has evolved and adapted to the temperate climate of the Pacific Northwest region of North America. This pathogen is now endemic and an increasingly common cause of life-threatening pulmonary and central nervous system infections that are difficult to manage and, in some cases, fatal to humans and other mammals throughout the region. A series of recent reports provide evidence that evolutionary, climatic, and anthropogenic factors may be causing the expansion of the Vancouver Island outbreak genotype into the United States, with the concomitant emergence of a unique genotype in the state of Oregon. Ongoing studies address the molecular epidemiology, roles of mating and genetic exchange, and geographic origins of this unprecedented outbreak of fungal infection of considerable public health magnitude.
doi:10.3410/B1-62
PMCID: PMC2818080  PMID: 20150950
8.  RecA-independent single-stranded DNA oligonucleotide-mediated mutagenesis 
F1000 biology reports  2010;2(1):56.
The expression of Beta, the single-stranded annealing protein (SSAP) of bacteriophage λ in Escherichia coli promotes high levels of oligonucleotide (oligo)-mediated mutagenesis and offers a quick way to create single or multiple base pair insertions, deletions, or substitutions in the bacterial chromosome. High rates of mutagenesis can be obtained by the use of mismatch repair (MMR)-resistant mismatches or MMR-deficient hosts, which allow for the isolation of unselected mutations. It has recently become clear that many bacteria can be mutagenized with oligos in the absence of any SSAP expression, albeit at a much lower frequency. Studies have shown that inactivation or inhibition of single-stranded DNA (ssDNA) exonucleases in vivo increases the rate of SSAP-independent oligo-mediated mutagenesis. These results suggest that λ Beta, in addition to its role in annealing the oligo to ssDNA regions of the replication fork, promotes high rates of oligo-mediated mutagenesis by protecting the oligo from destruction by host ssDNA exonucleases.
doi:10.3410/B2-56
PMCID: PMC2920528  PMID: 20711416
9.  Transport vesicle uncoating: it’s later than you think 
Transport vesicle coat proteins play active roles in vesicle cargo sorting as well as membrane deformation and fission during vesicle biogenesis. For years, it was assumed that this was the extent of the coats’ function and that the coats depolymerized immediately after vesicle budding, leaving the exposed fusion machinery free to find, dock, and fuse with the proper target membrane. Recently, however, it has become increasingly clear that the coat remains on transport vesicles during their post-budding life and in fact helps properly pair up the vesicle with its intended target membrane. These data have brought up urgent questions about exactly when vesicles do uncoat and how uncoating is regulated. Here, we summarize the latest round of evidence for post-budding roles for coats, including a few hints about how the uncoating process may be coupled to docking and fusion. We also speculate about the possibility of post-fusion functions for residual coats.
PMCID: PMC2919759  PMID: 20706600
10.  RecA-independent single-stranded DNA oligonucleotide-mediated mutagenesis 
The expression of Beta, the single-stranded annealing protein (SSAP) of bacteriophage λ in Escherichia coli promotes high levels of oligonucleotide (oligo)-mediated mutagenesis and offers a quick way to create single or multiple base pair insertions, deletions, or substitutions in the bacterial chromosome. High rates of mutagenesis can be obtained by the use of mismatch repair (MMR)-resistant mismatches or MMR-deficient hosts, which allow for the isolation of unselected mutations. It has recently become clear that many bacteria can be mutagenized with oligos in the absence of any SSAP expression, albeit at a much lower frequency. Studies have shown that inactivation or inhibition of single-stranded DNA (ssDNA) exonucleases in vivo increases the rate of SSAP-independent oligo-mediated mutagenesis. These results suggest that λ Beta, in addition to its role in annealing the oligo to ssDNA regions of the replication fork, promotes high rates of oligo-mediated mutagenesis by protecting the oligo from destruction by host ssDNA exonucleases.
doi:10.3410/B2-56
PMCID: PMC2920528  PMID: 20711416
11.  Brd4 engagement from chromatin targeting to transcriptional regulation: selective contact with acetylated histone H3 and H4 
Bromodomain-containing protein 4 (Brd4) contains two tandem bromodomains (BD1 and BD2) that bind preferentially to acetylated lysine residues found in histones and nonhistone proteins. This molecular recognition allows Brd4 to associate with acetylated chromatin throughout the cell cycle and regulates transcription at targeted loci. Recruitment of positive transcription elongation factor b, and possibly the general initiation cofactor Mediator as well, plays an important role in Brd4-regulated transcription. Selective contacts with acetyl-lysines in nucleosomal histones and chromatin-binding factors likely provide a molecular switch modulating the steps from chromatin targeting to transcriptional regulation, thus further expanding the ‘acetylation code’ for combinatorial regulation in eukaryotes.
doi:10.3410/B1-98
PMCID: PMC2873783  PMID: 20495683
12.  Transport vesicle uncoating: it’s later than you think 
Transport vesicle coat proteins play active roles in vesicle cargo sorting as well as membrane deformation and fission during vesicle biogenesis. For years, it was assumed that this was the extent of the coats’ function and that the coats depolymerized immediately after vesicle budding, leaving the exposed fusion machinery free to find, dock, and fuse with the proper target membrane. Recently, however, it has become increasingly clear that the coat remains on transport vesicles during their post-budding life and in fact helps properly pair up the vesicle with its intended target membrane. These data have brought up urgent questions about exactly when vesicles do uncoat and how uncoating is regulated. Here, we summarize the latest round of evidence for post-budding roles for coats, including a few hints about how the uncoating process may be coupled to docking and fusion. We also speculate about the possibility of post-fusion functions for residual coats.
doi:10.3410/B2-47
PMCID: PMC2919759  PMID: 20706600
13.  Latest advances in innate antiviral defence 
F1000 biology reports  2009;1(22):nihpa103883.
Recent identification of key components in the pattern recognition receptor pathway of retinoic acid-inducible gene-1-like receptors, coupled with characterisation of a new cytoplasmic DNA-sensing molecule, have led to a greater understanding of the role viral nucleic acids play in activating innate immunity. This activation of type I interferon is essential for both limiting viral infection and stimulating activation of the adaptive immune response.
doi:10.3410/B1-22
PMCID: PMC2773505  PMID: 20160888
14.  Brd4 engagement from chromatin targeting to transcriptional regulation: selective contact with acetylated histone H3 and H4 
Bromodomain-containing protein 4 (Brd4) contains two tandem bromodomains (BD1 and BD2) that bind preferentially to acetylated lysine residues found in histones and nonhistone proteins. This molecular recognition allows Brd4 to associate with acetylated chromatin throughout the cell cycle and regulates transcription at targeted loci. Recruitment of positive transcription elongation factor b, and possibly the general initiation cofactor Mediator as well, plays an important role in Brd4-regulated transcription. Selective contacts with acetyl-lysines in nucleosomal histones and chromatin-binding factors likely provide a molecular switch modulating the steps from chromatin targeting to transcriptional regulation, thus further expanding the ‘acetylation code’ for combinatorial regulation in eukaryotes.
doi:10.3410/B1-98
PMCID: PMC2873783  PMID: 20495683
15.  Osmolyte solutions and protein folding 
F1000 biology reports  2009;1(41):1-3.
In this brief review we discuss the evolution of recent thought regarding the role and mechanism of osmolytes with respect to protein stability. Osmolytes are naturally occurring intracellular compounds that change the protein folding landscape. Contributions from experiments are considered in the context of current theory and simulation results.
doi:10.3410/B1-41
PMCID: PMC2786071  PMID: 19960095
16.  The evolving story of orexin biology: the hits keep coming 
In the span of just 11 years since their discovery, the study of the orexins (hypocretins) has not only provided insight into the biology of sleep/wakefulness, but also demonstrated the importance of the development of new pharmacologic tools and genetic models with which to understand basic physiologic mechanisms and provide potential strategies for the treatment of human pathologies. Highlights from recently published novel approaches and findings are reviewed here.
doi:10.3410/B1-85
PMCID: PMC2886298  PMID: 20563314
17.  Conformational changes in receptor tyrosine kinase signaling: an ErbB garden of delights 
The ErbB family of receptor tyrosine kinases plays important roles in cell proliferation, differentiation, and apoptosis. Recent structural studies of these receptors have demonstrated dramatic conformational effects that are critical to their ligand binding and activation, and have shown that these receptors provide levels of control beyond the classic dimerization/activation mechanism. These results indicate that this class of receptors has evolved subtle regulatory mechanisms via genetic and protein structural changes to influence their effects on cell behaviors.
doi:10.3410/B1-72
PMCID: PMC2847299  PMID: 20357902
18.  Diversity of protein structures and difficulties in fold recognition: the curious case of protein G 
We examine the ability of current state-of-the-art methods in protein structure prediction to discriminate topologically distant folds encoded by highly similar (>90% sequence identity) designed proteins in blind protein structure prediction experiments. We detail the corresponding prognosis for the protein fold recognition field and highlight the features of the methodologies that successfully deciphered this folding riddle.
doi:10.3410/B1-69
PMCID: PMC2832337  PMID: 20209018
19.  Do apicomplexan parasite-encoded proteins act as both ligands and receptors during host cell invasion? 
Apicomplexan parasites are responsible for a wide range of diseases in animals, including humans, in whom Plasmodium species cause the devastating disease malaria. Several recent discoveries now indicate that these intracellular parasites may use a conserved mechanism to infect their host cells by using parasite-encoded proteins as both parasite ligands and receptors anchored to the host cells.
doi:10.3410/B1-64
PMCID: PMC2832315  PMID: 20209017
20.  Vesicle coating and uncoating: controlling the formation of large COPII-coated carriers 
The basic mechanisms underlying the formation of coated vesicles are now defined in considerable detail. This article highlights recent developments in our understanding of the problem of exporting large macromolecular cargo such as procollagen from the endoplasmic reticulum and discusses the implications that this has for cell and tissue organisation and human disease.
doi:10.3410/B1-65
PMCID: PMC2854804  PMID: 20401317
21.  Setting the absolute threshold of vision 
The performance of sensory systems in many cases is limited by the physical nature of the stimulus. For vision, the quantal nature of light limits detection by dark-adapted observers; only now are we beginning to be aware of the subtleties in the biophysical mechanisms underlying this exquisite sensitivity.
doi:10.3410/B1-66
PMCID: PMC2873777  PMID: 20495680
22.  Cryptococcus gattii outbreak expands into the Northwestern United States with fatal consequences 
In the past decade, the primary fungal pathogen Cryptococcus gattii has evolved and adapted to the temperate climate of the Pacific Northwest region of North America. This pathogen is now endemic and an increasingly common cause of life-threatening pulmonary and central nervous system infections that are difficult to manage and, in some cases, fatal to humans and other mammals throughout the region. A series of recent reports provide evidence that evolutionary, climatic, and anthropogenic factors may be causing the expansion of the Vancouver Island outbreak genotype into the United States, with the concomitant emergence of a unique genotype in the state of Oregon. Ongoing studies address the molecular epidemiology, roles of mating and genetic exchange, and geographic origins of this unprecedented outbreak of fungal infection of considerable public health magnitude.
doi:10.3410/B1-62
PMCID: PMC2818080  PMID: 20150950
23.  Osmolyte solutions and protein folding 
In this brief review we discuss the evolution of recent thought regarding the role and mechanism of osmolytes with respect to protein stability. Osmolytes are naturally occurring intracellular compounds that change the protein folding landscape. Contributions from experiments are considered in the context of current theory and simulation results.
doi:10.3410/B1-41
PMCID: PMC2786071  PMID: 19960095
24.  Latest advances in innate antiviral defence 
Recent identification of key components in the pattern recognition receptor pathway of retinoic acid-inducible gene-1-like receptors, coupled with the characterisation of a new cytoplasmic DNA-sensing molecule, has led to a greater understanding of the role that viral nucleic acids play in activating innate immunity. This activation of type-I interferon is essential for both limiting viral infection and stimulating activation of the adaptive immune response.
doi:10.3410/B1-22
PMCID: PMC2773505  PMID: 20160888

Results 1-24 (24)