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https://www.readbyqxmd.com/read/27926995/frozen-but-no-accident-why-the-20-standard-amino-acids-were-selected
#1
REVIEW
Andrew J Doig
The 20 standard amino acids encoded by the Genetic Code were adopted during the RNA World, around 4 billion years ago. This amino acid set could be regarded as a frozen accident, implying that other possible structures could equally well have been chosen to use in proteins. Amino acids were not primarily selected for their ability to support catalysis, since the RNA World already had highly effective cofactors to perform reactions, such as oxidation, reduction and transfer of small molecules. Rather, they were selected to enable the formation of soluble structures with close-packed cores, allowing the presence of ordered binding pockets...
December 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27926992/inherited-diseases-caused-by-mutations-in-cathepsin-protease-genes
#2
REVIEW
Stephanie Ketterer, Alejandro Gomez-Auli, Larissa E Hillebrand, Agnese Petrera, Anett Ketscher, Thomas Reinheckel
Lysosomal cathepsins are proteolytic enzymes increasingly recognized as prognostic markers and potential therapeutic targets in a variety of diseases. In those conditions the cathepsins are mostly overexpressed, thereby driving the respective pathogenic processes. Although less known, there are also diseases with a genetic deficiency of cathepsins. In fact, nowadays six out of the fifteen human proteases called "cathepsins" have been linked to inherited syndromes. However, only three of these syndromes are typical lysosomal storage diseases, while the others are apparently caused by defective cleavage of specific protein substrates...
December 7, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27926970/management-of-endometriosis-involving-the-urinary-tract
#3
Mobolaji O Ajao, Jon I Einarsson
Endometriosis is a common cause of infertility and disabling pelvic pain in reproductive age women. The most widely accepted theory of its pathogenesis is the retrograde flow of menstrual products, although extra-abdominal and extrapelvic diagnoses have been made. After the pelvic peritoneum and gynecologic structures, the most commonly affected sites are the lower gastrointestinal and urinary tracts. When the urinary tract is involved, the bladder is the predominant site, followed by the ureters. The focus of this seminar will thus be these two anatomic sites...
December 7, 2016: Seminars in Reproductive Medicine
https://www.readbyqxmd.com/read/27926950/c6-and-c7-substituted-3-4-dihydro-2-1h-quinolinones-as-inhibitors-of-monoamine-oxidase
#4
L Meiring, J Petzer, A Petzer
Purpose Monoamine oxidase (MAO) inhibitors are considered to be useful therapeutic agents and isoform specific inhibitors are employed for the treatment of depression and Parkinson's disease. MAO inhibitors are also under investigation for the treatment of disorders ranging from Alzheimer's disease, prostate cancer and certain cardiomyopathies. While a number of irreversible MAO inhibitors are available in the clinic, reversible inhibitors, particularly of the MAO-B isoform are still being developed. Based on our interest in discovering reversible inhibitors with specificity for MAO-B, we have recently reported that, among a series of 10 3,4-dihydro-2(1H)-quinolinone derivatives, are high potency MAO-B inhibitors, with a number of homologues displaying good selectivities for MAO-B over the MAO-A isoform...
December 7, 2016: Drug Research
https://www.readbyqxmd.com/read/27926945/ear-structures-of-the-naked-mole-rat-heterocephalus-glaber-and-its-relatives-rodentia-bathyergidae
#5
Matthew J Mason, Hannah L Cornwall, Ewan St J Smith
Although increasingly popular as a laboratory species, very little is known about the peripheral auditory system of the naked mole-rat, Heterocephalus glaber. In this study, middle and inner ears of naked mole-rats of a range of ages were examined using micro-computed tomography and dissection. The ears of five other bathyergid species (Bathyergus suillus, Cryptomys hottentotus, Fukomys micklemi, Georychus capensis and Heliophobius argenteocinereus) were examined for comparative purposes. The middle ears of bathyergids show features commonly found in other members of the Ctenohystrica rodent clade, including a fused malleus and incus, a synovial stapedio-vestibular articulation and the loss of the stapedius muscle...
2016: PloS One
https://www.readbyqxmd.com/read/27926939/a-bystander-mechanism-explains-the-specific-phenotype-of-a-broadly-expressed-misfolded-protein
#6
Lauren Klabonski, Ji Zha, Lakshana Senthilkumar, Tali Gidalevitz
Misfolded proteins in transgenic models of conformational diseases interfere with proteostasis machinery and compromise the function of many structurally and functionally unrelated metastable proteins. This collateral damage to cellular proteins has been termed 'bystander' mechanism. How a single misfolded protein overwhelms the proteostasis, and how broadly-expressed mutant proteins cause cell type-selective phenotypes in disease are open questions. We tested the gain-of-function mechanism of a R37C folding mutation in an endogenous IGF-like C...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27926936/scaling-properties-of-dimensionality-reduction-for-neural-populations-and-network-models
#7
Ryan C Williamson, Benjamin R Cowley, Ashok Litwin-Kumar, Brent Doiron, Adam Kohn, Matthew A Smith, Byron M Yu
Recent studies have applied dimensionality reduction methods to understand how the multi-dimensional structure of neural population activity gives rise to brain function. It is unclear, however, how the results obtained from dimensionality reduction generalize to recordings with larger numbers of neurons and trials or how these results relate to the underlying network structure. We address these questions by applying factor analysis to recordings in the visual cortex of non-human primates and to spiking network models that self-generate irregular activity through a balance of excitation and inhibition...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27926928/an-interactome-centered-protein-discovery-approach-reveals-novel-components-involved-in-mitosome-function-and-homeostasis-in-giardia-lamblia
#8
Samuel Rout, Jon Paulin Zumthor, Elisabeth M Schraner, Carmen Faso, Adrian B Hehl
Protozoan parasites of the genus Giardia are highly prevalent globally, and infect a wide range of vertebrate hosts including humans, with proliferation and pathology restricted to the small intestine. This narrow ecological specialization entailed extensive structural and functional adaptations during host-parasite co-evolution. An example is the streamlined mitosomal proteome with iron-sulphur protein maturation as the only biochemical pathway clearly associated with this organelle. Here, we applied techniques in microscopy and protein biochemistry to investigate the mitosomal membrane proteome in association to mitosome homeostasis...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926874/multivalent-histone-and-dna-engagement-by-a-phd-brd-pwwp-triple-reader-cassette-recruits-zmynd8-to-k14ac-rich-chromatin
#9
Pavel Savitsky, Tobias Krojer, Takao Fujisawa, Jean-Philippe Lambert, Sarah Picaud, Chen-Yi Wang, Erin K Shanle, Krzysztof Krajewski, Hans Friedrichsen, Alexander Kanapin, Colin Goding, Matthieu Schapira, Anastasia Samsonova, Brian D Strahl, Anne-Claude Gingras, Panagis Filippakopoulos
Elucidation of interactions involving DNA and histone post-translational-modifications (PTMs) is essential for providing insights into complex biological functions. Reader assemblies connected by flexible linkages facilitate avidity and increase affinity; however, little is known about the contribution to the recognition process of multiple PTMs because of rigidity in the absence of conformational flexibility. Here, we resolve the crystal structure of the triple reader module (PHD-BRD-PWWP) of ZMYND8, which forms a stable unit capable of simultaneously recognizing multiple histone PTMs while presenting a charged platform for association with DNA...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926869/robust-asymmetric-localization-of-planar-polarity-proteins-is-associated-with-organization-into-signalosome-like-domains-of-variable-stoichiometry
#10
Helen Strutt, Jessica Gamage, David Strutt
In developing epithelia, the core planar polarity proteins physically interact with each other and localize asymmetrically at opposite cell ends, forming intercellular complexes that link the polarity of neighboring cells. Using quantitative imaging to examine the composition of the core protein complex in vivo, we find that complex composition is unexpectedly plastic. The transmembrane proteins Frizzled and Flamingo form a stoichiometric nucleus in the complex, while the relative levels of the other four core proteins can vary independently...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926854/structural-characterization-and-statistical-mechanical-model-of-epidermal-patterns
#11
Duyu Chen, Wen Yih Aw, Danelle Devenport, Salvatore Torquato
In proliferating epithelia of mammalian skin, cells of irregular polygon-like shapes pack into complex, nearly flat two-dimensional structures that are pliable to deformations. In this work, we employ various sensitive correlation functions to quantitatively characterize structural features of evolving packings of epithelial cells across length scales in mouse skin. We find that the pair statistics in direct space (correlation function) and Fourier space (structure factor) of the cell centroids in the early stages of embryonic development show structural directional dependence (statistical anisotropy), which is a reflection of the fact that cells are stretched, which promotes uniaxial growth along the epithelial plane...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926849/effects-of-dimethyl-sulfoxide-on-surface-water-near-phospholipid-bilayers
#12
Yuno Lee, Philip A Pincus, Changbong Hyeon
Despite much effort to probe the properties of dimethyl sulfoxide (DMSO) solution, the effects of DMSO on water, especially near plasma membrane surfaces, still remain elusive. By performing molecular dynamics simulations at varying DMSO concentrations (XDMSO), we study how DMSO affects structural and dynamical properties of water in the vicinity of phospholipid bilayers. As proposed by a number of experiments, our simulations confirm that DMSO induces dehydration from bilayer surfaces and disrupts the H-bond structure of water...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926847/probing-lipid-bilayers-under-ionic-imbalance
#13
Jiaqi Lin, Alfredo Alexander-Katz
Biological membranes are normally under a resting transmembrane potential (TMP), which originates from the ionic imbalance between extracellular fluids and cytosols, and serves as electric power storage for cells. In cell electroporation, the ionic imbalance builds up a high TMP, resulting in the poration of cell membranes. However, the relationship between ionic imbalance and TMP is not clearly understood, and little is known about the effect of ionic imbalance on the structure and dynamics of biological membranes...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926846/alamethicin-supramolecular-organization-in-lipid-membranes-from-19-f-solid-state-nmr
#14
Evgeniy S Salnikov, Jesus Raya, Marta De Zotti, Ekaterina Zaitseva, Cristina Peggion, Gema Ballano, Claudio Toniolo, Jan Raap, Burkhard Bechinger
Alamethicins (ALMs) are antimicrobial peptides of fungal origin. Their sequences are rich in hydrophobic amino acids and strongly interact with lipid membranes, where they cause a well-defined increase in conductivity. Therefore, the peptides are thought to form transmembrane helical bundles in which the more hydrophilic residues line a water-filled pore. Whereas the peptide has been well characterized in terms of secondary structure, membrane topology, and interactions, much fewer data are available regarding the quaternary arrangement of the helices within lipid bilayers...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926843/membrane-anchoring-and-ion-entry-dynamics-in-p-type-atpase-copper-transport
#15
Christina Grønberg, Oleg Sitsel, Erik Lindahl, Pontus Gourdon, Magnus Andersson
Cu(+)-specific P-type ATPase membrane protein transporters regulate cellular copper levels. The lack of crystal structures in Cu(+)-binding states has limited our understanding of how ion entry and binding are achieved. Here, we characterize the molecular basis of Cu(+) entry using molecular-dynamics simulations, structural modeling, and in vitro and in vivo functional assays. Protein structural rearrangements resulting in the exposure of positive charges to bulk solvent rather than to lipid phosphates indicate a direct molecular role of the putative docking platform in Cu(+) delivery...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926842/intact-telopeptides-enhance-interactions-between-collagens
#16
Marjan Shayegan, Tuba Altindal, Evan Kiefl, Nancy R Forde
Collagen is the fundamental structural component of a wide range of connective tissues and of the extracellular matrix. It undergoes self-assembly from individual triple-helical proteins into well-ordered fibrils, a process that is key to tissue development and homeostasis, and to processes such as wound healing. Nucleation of this assembly is known to be slowed considerably by pepsin removal of short nonhelical regions that flank collagen's triple helix, known as telopeptides. Using optical tweezers to perform microrheology measurements, we explored the changes in viscoelasticity of solutions of collagen with and without intact telopeptides...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926841/broken-tales-transcription-activator-like-effectors-populate-partly-folded-states
#17
Kathryn Geiger-Schuller, Doug Barrick
Transcription activator-like effector proteins (TALEs) contain large numbers of repeats that bind double-stranded DNA, wrapping around DNA to form a continuous superhelix. Since unbound TALEs retain superhelical structure, it seems likely that DNA binding requires a significant structural distortion or partial unfolding. In this study, we use nearest-neighbor "Ising" analysis of consensus TALE (cTALE) repeat unfolding to quantify intrinsic folding free energies, coupling energies between repeats, and the free energy distribution of partly unfolded states, and to determine how those energies depend on the sequence that determines DNA-specificity (called the "RVD")...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926840/calcium-dependent-structural-dynamics-of-a-spin-labeled-ryr-peptide-bound-to-calmodulin
#18
Cheng Her, Jesse E McCaffrey, David D Thomas, Christine B Karim
We have used chemical synthesis, electron paramagnetic resonance (EPR), and circular dichroism to detect and analyze the structural dynamics of a ryanodine receptor (RyR) peptide bound to calmodulin (CaM). The skeletal muscle calcium release channel RyR1 is activated by Ca(2+)-free CaM and inhibited by Ca(2+)-bound CaM. To probe the structural mechanism for this regulation, wild-type RyRp and four spin-labeled derivatives were synthesized, each containing the nitroxide probe 2,2,6,6-tetramethyl-piperidine-1-oxyl-4-amino-4-carboxylic acid substituted for a single amino acid...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926839/circular-dichroism-spectroscopy-of-collagen-fibrillogenesis-a-new-use-for-an-old-technique
#19
Kathryn E Drzewiecki, Daniel R Grisham, Avanish S Parmar, Vikas Nanda, David I Shreiber
Type-I collagen assembles in a stepwise, hierarchic fashion from the folding of the triple helix to the assembly of fibrils into fibers. The mature assembled fibers are crucial for tissue structure and mechanics, cell interactions, and other functions in vivo. Although triple helix folding can be followed with the use of optical methods such as circular dichroism (CD) spectroscopy, fibrillogenesis is typically measured by alternative methods such as turbidity, rheology, and microscopy. Together, these approaches allow for investigation of the mechanical properties and architectures of collagen-based scaffolds and excised tissues...
December 6, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/27926838/high-resolution-mapping-of-a-repeat-protein-folding-free-energy-landscape
#20
Martin J Fossat, Thuy P Dao, Kelly Jenkins, Mariano Dellarole, Yinshan Yang, Scott A McCallum, Angel E Garcia, Doug Barrick, Christian Roumestand, Catherine A Royer
A complete description of the pathways and mechanisms of protein folding requires a detailed structural and energetic characterization of the conformational ensemble along the entire folding reaction coordinate. Simulations can provide this level of insight for small proteins. In contrast, with the exception of hydrogen exchange, which does not monitor folding directly, experimental studies of protein folding have not yielded such structural and energetic detail. NMR can provide residue specific atomic level structural information, but its implementation in protein folding studies using chemical or temperature perturbation is problematic...
December 6, 2016: Biophysical Journal
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