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Zuriñe Antón, Ane Landajuela, Javier H Hervás, L Ruth Montes, Sonia Hernández-Tiedra, Guillermo Velasco, Felix M Goñi, Alicia Alonso
The phospholipid cardiolipin (CL) has been proposed to play a role in selective mitochondrial autophagy, or mitophagy. CL externalization to the outer mitochondrial membrane would act as a signal for the human Atg8 ortholog subfamily, MAP1LC3 (LC3). The latter would mediate both mitochondrial recognition and autophagosome formation, ultimately leading to removal of damaged mitochondria. We have applied quantitative biophysical techniques to the study of CL interaction with various Atg8 human orthologs, namely LC3B, GABARAPL2 and GABARAP...
October 20, 2016: Autophagy
Lucas C Wheeler, Micah T Donor, James S Prell, Michael J Harms
The S100 proteins are a large family of signaling proteins that play critical roles in biology and disease. Many S100 proteins bind Zn2+, Cu2+, and/or Mn2+ as part of their biological functions; however, the evolutionary origins of binding remain obscure. One key question is whether divalent transition metal binding is ancestral, or instead arose independently on multiple lineages. To tackle this question, we combined phylogenetics with biophysical characterization of modern S100 proteins. We demonstrate an earlier origin for established S100 subfamilies than previously believed, and reveal that transition metal binding is widely distributed across the tree...
2016: PloS One
Jessica A Flynn, Eberhard Durr, Ryan Swoyer, Pedro J Cejas, Melanie S Horton, Jennifer D Galli, Scott A Cosmi, Amy S Espeseth, Andrew J Bett, Lan Zhang
Infection with Respiratory Syncytial Virus (RSV) causes both upper and lower respiratory tract disease in humans, leading to significant morbidity and mortality in both young children and older adults. Currently, there is no licensed vaccine available, and therapeutic options are limited. During the infection process, the type I viral fusion (F) glycoprotein on the surface of the RSV particle rearranges from a metastable prefusion conformation to a highly stable postfusion form. In people naturally infected with RSV, most potent neutralizing antibodies are directed to the prefusion form of the F protein...
2016: PloS One
Xin Tian, Zaixing Yang, Guangxin Duan, Anqing Wu, Zonglin Gu, Leili Zhang, Chunying Chen, Zhifang Chai, Cuicui Ge, Ruhong Zhou
Graphene and graphene-based nanomaterials are broadly used for various biomedical applications due to their unique physiochemical properties. However, how graphene-based nanomaterials interact with biological systems has not been thoroughly studied. This study shows that graphene oxide (GO) nanosheets retard A549 lung carcinoma cell migration through nanosheet-mediated disruption of intracellular actin filaments. After GO nanosheets treatment, A549 cells display slower migration and the structure of the intracellular actin filaments is dramatically changed...
October 20, 2016: Small
Nirod Kumar Sarangi, K G Ayappa, Sandhya S Visweswariah, Jaydeep Kumar Basu
Cell membranes are believed to be highly complex dynamical systems having compositional heterogeneity involving several types of lipids and proteins as the major constituents. This dynamical and compositional heterogeneity is suggested to be critical to the maintenance of active functionality and response to chemical, mechanical, electrical and thermal stresses. However, delineating the various factors responsible for the spatio-temporal response of actual cell membranes to stresses can be quite challenging...
October 20, 2016: Physical Chemistry Chemical Physics: PCCP
Sonia Fieulaine, Rodolphe Alves de Sousa, Laure Maigre, Karim Hamiche, Mickael Alimi, Jean-Michel Bolla, Abbass Taleb, Alexis Denis, Jean-Marie Pagès, Isabelle Artaud, Thierry Meinnel, Carmela Giglione
Peptide deformylase (PDF) is considered an excellent target to develop antibiotics. We have performed an extensive characterization of a new PDF from the pathogen Streptococcus agalactiae, showing properties similar to other known PDFs. S. agalactiae PDF could be used as PDF prototype as it allowed to get complete sets of 3-dimensional, biophysical and kinetic data with virtually any inhibitor compound. Structure-activity relationship analysis with this single reference system allowed us to reveal distinct binding modes for different PDF inhibitors and the key role of a hydrogen bond in potentiating the interaction between ligand and target...
October 20, 2016: Scientific Reports
Somnath Mukherjee, Jayanta Chatterjee
Despite a number of intriguing utilities associated with thioamide-containing peptides and proteins in the context of biophysics, pharmacology and chemical biology, it has hitherto remained as one of the underexplored territories of peptidomimetics. The synthesis of long mono to multiply substituted endothioamide peptides is invariably accompanied with severe epimerization, oxoamide formation and various other undesired side reactions, resulting in messy product profiles. This has completely restrained their use as novel chemical tools for biological studies...
October 20, 2016: Journal of Peptide Science: An Official Publication of the European Peptide Society
Laura Acquasaliente, Daniele Peterle, Simone Tescari, Nicola Pozzi, Vittorio Pengo, Vincenzo De Filippis
: β2-Glycoprotein I (β2GpI) is the major autoantigen in the antiphospholipid syndrome, a thrombotic autoimmune disease. Nonetheless, the physiological role of β2GpI is still unclear. In a recent work, we have shown that β2GpI selectively inhibits the procoagulant functions of human a-thrombin (αT) (i.e. prolongs fibrin clotting time, tc, and inhibits αT-induced platelets aggregation) without affecting the unique anticoagulant activity of the protease, i.e. the proteolytic generation of the anticoagulant protein C (PC) from the PC zymogen, which interacts with αT exclusively at the protease catalytic site...
October 19, 2016: Biochemical Journal
Jelle Hendrix, Tomas Dekens, Waldemar Schrimpf, Don C Lamb
Combining imaging with correlation spectroscopy, as in raster image correlation spectroscopy (RICS), makes it possible to extract molecular translational diffusion constants and absolute concentrations, and determine intermolecular interactions from single-channel or multicolor confocal laser-scanning microscopy (CLSM) images. Region-specific RICS analysis remains very challenging because correlations are always calculated in a square region-of-interest (ROI). In this study, we describe a generalized image correlation spectroscopy algorithm that accepts arbitrarily shaped ROIs...
October 18, 2016: Biophysical Journal
Tom Bongiorno, Jena L Chojnowski, James D Lauderdale, Todd Sulchek
Healthy eyes contain a population of limbal stem cells (LSCs) that continuously renew the corneal epithelium. However, each year, 1 million Americans are afflicted with severely reduced visual acuity caused by corneal damage or disease, including LSC deficiency (LSCD). Recent advances in corneal transplant technology promise to repair the cornea by implanting healthy LSCs to encourage regeneration; however, success is limited to transplanted tissues that contain a sufficiently high percentage of LSCs. Attempts to screen limbal tissues for suitable implants using molecular stemness markers are confounded by the poorly understood signature of the LSC phenotype...
October 18, 2016: Biophysical Journal
Maite L Ortiz-Suarez, Firdaus Samsudin, Thomas J Piggot, Peter J Bond, Syma Khalid
OmpA is a multidomain protein found in the outer membranes of most Gram-negative bacteria. Despite a wealth of reported structural and biophysical studies, the structure-function relationships of this protein remain unclear. For example, it is still debated whether it functions as a pore, and the precise molecular role it plays in attachment to the peptidoglycan of the periplasm is unknown. The absence of a consensus view is partly due to the lack of a complete structure of the full-length protein. To address this issue, we performed molecular-dynamics simulations of the full-length model of the OmpA dimer proposed by Robinson and co-workers...
October 18, 2016: Biophysical Journal
Nabanita Das, Varun Dewan, Peter M Grace, Robin J Gunn, Ryo Tamura, Netanel Tzarum, Linda R Watkins, Ian A Wilson, Hang Yin
Infectious and sterile inflammatory diseases are correlated with increased levels of high mobility group box 1 (HMGB1) in tissues and serum. Extracellular HMGB1 is known to activate Toll-like receptors (TLRs) 2 and 4 and RAGE (receptor for advanced glycation endproducts) in inflammatory conditions. Here, we find that TLR5 is also an HMGB1 receptor that was previously overlooked due to lack of functional expression in the cell lines usually used for studying TLR signaling. HMGB1 binding to TLR5 initiates the activation of NF-κB signaling pathway in a MyD88-dependent manner, resulting in proinflammatory cytokine production and pain enhancement in vivo...
October 18, 2016: Cell Reports
Shaltiel Eloul, Richard G Compton
The diffusion of a particle from bulk solution is slowed as it moves close to an adsorbing surface. A general model is reported which is easily applied by theoreticians and experimentalists. Specifically, it is shown here that in general and regardless of the space size, the magnitude of the effect of hindered diffusion on the flux is a property of the diffusion layer thickness. We quantify and explain the effect. Predictions of concentration profiles show that a 'hindered diffusion layer' is formed near the adsorbing surface within the diffusion layer, observed even when the particle radius is just a 0...
October 19, 2016: Journal of Physical Chemistry Letters
Mingming Wang, Wei Zhan
The grand scale, ultimate efficiency, and sustainability of natural photosynthesis have inspired generations of researchers in biomimetic light energy utilization. As an essential and ubiquitous component in all photosynthetic machinery, lipids and their assemblies have long been recognized as powerful molecular scaffolds in building artificial photosynthetic systems. Model lipid bilayers, such as black lipid membranes and liposomes (vesicles), have been extensively used to host natural as well as synthetic photo- and redox-active species, thereby enabling key photosynthetic processes, such as energy transfer and photoinduced electron transfer, to be examined in well-defined, natural-like membrane settings...
October 19, 2016: Accounts of Chemical Research
A Andrade, J Hope, A Allen, V Yorgan, D Lipscombe, J Q Pan
CACNA1I is a candidate schizophrenia risk gene. It encodes the pore-forming human CaV3.3 α1 subunit, a subtype of voltage-gated calcium channel that contributes to T-type currents. Recently, two de novo missense variations, T797M and R1346H, of hCaV3.3 were identified in individuals with schizophrenia. Here we show that R1346H, but not T797M, is associated with lower hCaV3.3 protein levels, reduced glycosylation, and lower membrane surface levels of hCaV3.3 when expressed in human cell lines compared to wild-type...
October 19, 2016: Scientific Reports
Sanjay Kumar Dey, Pankaj Prabhakar, Manisha Saini, Toyanji Joseph, B K Thelma, Subir K Maulik, Suman Kundu
OBJECTIVE: To identify novel inhibitors of dopamine beta hydroxylase (DBH) and evaluate their antihypertensive properties in L-NAME induced hypertensive rat model. DESIGN AND METHOD: An experimentally validated computational model for hDBH, built in our lab, was used for structure-based, rational drug-design. The three-dimensional model was used for virtual-screening against small molecule databases from NCI, USA and elsewhere. Identified top hits were then tested in vitro against DBH with known inhibitors nepicastat and disulfiram as controls...
September 2016: Journal of Hypertension
Michal Behuliak, Michal Bencze, Anna Vavrinova, Ivana Vaneckova, Josef Zicha
OBJECTIVE: Voltage-dependent calcium channels (VDCCs) play an important role in two major abnormalities observed in spontaneously hypertensive rats (SHR) - hyperactivity of sympathetic nervous system (SNS) and enhanced Ca influx to vascular smooth muscle cells (VSMC). α2δ subunit of VDCC, which promotes surface trafficking and modulates the biophysical properties of VDCC, was identified as a critical component of increased L-type VDCC calcium currents in arterial myocytes of SHR. On the other hand, N-type VDCCs control a neurotransmitter release in the peripheral sympathetic nervous system and play an important role in sympathetic hyperactivity in SHR...
September 2016: Journal of Hypertension
Martina F Callaghan, Siawoosh Mohammadi, Nikolaus Weiskopf
Quantitative MRI (qMRI) provides standardized measures of specific physical parameters that are sensitive to the underlying tissue microstructure and are a first step towards achieving maps of biologically relevant metrics through in vivo histology using MRI. Recently proposed models have described the interdependence of qMRI parameters. Combining such models with the concept of image synthesis points towards a novel approach to synthetic qMRI, in which maps of fundamentally different physical properties are constructed through the use of biophysical models...
October 18, 2016: NMR in Biomedicine
B Bonito, D R P Sauter, A Schwab, M B A Djamgoz, I Novak
In the recent decades, ion channels became the focus of cancer biologists, as many channels are overexpressed in tumour tissue and functionally they are linked to abnormal cell behaviour with processes including apoptosis, chemo- and radioresistance, proliferation and migration. KCa3.1 is a Ca(2+)-activated K(+) channel that plays a central role in tumour progression in many cancer types. Therefore, the aim of the present study was to investigate KCa3.1 expression in pancreatic cancer cells and assess possible implications to disease progression...
October 17, 2016: Pflügers Archiv: European Journal of Physiology
Himanshu Pandey, Sarita Tripathi, Kanchan Srivastava, Dinesh K Tripathi, Mrigank Srivastava, Surya Kant, Kishore K Srivastava, Ashish Arora
BACKGROUND: We have characterized two immunogenic proteins, Rv1197 and Rv1198, of the Esx-5 system of the ESAT-6 family of Mycobacterium tuberculosis H37Rv. METHODS: The complex formation between Rv1197 and Rv1198 was characterized by biophysical techniques. The reactivity of serum from TB patients towards these proteins was characterized by ELISA. Lymphocyte proliferation and cytokine induction were followed in restimulated splenocytes from immunized mice by using MTT assay and CBA flowcytometry, respectively...
October 14, 2016: Biochimica et Biophysica Acta
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