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protein stability

Ioly Kotta-Loizou, Spyridon N Vasilopoulos, Robert H A Coutts, Stamatios Theocharis
Hu-antigen R (HuR) is an RNA-binding posttranscriptional regulator that belongs to the Hu/ELAV family. HuR expression levels are modulated by a variety of proteins, microRNAs, chemical compounds, or the microenvironment, and in turn, HuR affects mRNA stability and translation of various genes implicated in breast cancer formation, progression, metastasis, and treatment. The aim of the present review is to critically summarize the role of HuR in breast cancer development and its potential as a prognosticator and a therapeutic target...
October 17, 2016: Neoplasia: An International Journal for Oncology Research
Suman Kumar Nandy, Alpana Seal
Cystatin superfamily is a large group of evolutionarily related proteins involved in numerous physiological activities through their inhibitory activity towards cysteine proteases. Despite sharing the same cystatin fold, and inhibiting cysteine proteases through the same tripartite edge involving highly conserved N-terminal region, L1 and L2 loop; cystatins differ widely in their inhibitory affinity towards C1 family of cysteine proteases and molecular details of these interactions are still elusive. In this study, inhibitory interactions of human family 1 & 2 cystatins with cathepsin L1 are predicted and their stability and viability are verified through protein docking & comparative molecular dynamics...
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
Flavia A Mercurio, Daniela Marasco, Concetta Di Natale, Luciano Pirone, Susan Costantini, Emilia M Pedone, Marilisa Leone
The EphA2 receptor controls diverse physiological and pathological conditions and its levels are often upregulated in cancer. Targeting receptor overexpression, through modulation of endocytosis and consequent degradation, appears to be an appealing strategy for attacking tumor malignancy. In this scenario, the Sam domain of EphA2 plays a pivotal role because it is the site where protein regulators of endocytosis and stability are recruited by means of heterotypic Sam-Sam interactions. Because EphA2-Sam heterotypic complexes are largely based on electrostatic contacts, we have investigated the possibility of attacking these interactions with helical peptides enriched in charged residues...
October 20, 2016: Chembiochem: a European Journal of Chemical Biology
Agnieszka Mierczynska-Vasilev, Paul A Smith
The adsorption of macromolecules on solid surfaces is of great importance in the field of nanotechnology, biomaterials, biotechnological, and food processes. In the field of oenology adsorption of wine macromolecules such as polyphenols, polysaccharides, and proteins is much less desirable on membrane materials because of fouling and reduced filtering performance. On the other hand, adsorption of these molecules on processing aids is very beneficial for achieving wine clarity and stability. In this article, the effect of surface chemical functionalities on the adsorption of white, rosé, and red wine constituents was evaluated...
October 18, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Jacek Dygut, Barbara Kalinowska, Mateusz Banach, Monika Piwowar, Leszek Konieczny, Irena Roterman
The presented analysis concerns the inter-domain and inter-protein interface in protein complexes. We propose extending the traditional understanding of the protein domain as a function of local compactness with an additional criterion which refers to the presence of a well-defined hydrophobic core. Interface areas in selected homodimers vary with respect to their contribution to share as well as individual (domain-specific) hydrophobic cores. The basic definition of a protein domain, i.e., a structural unit characterized by tighter packing than its immediate environment, is extended in order to acknowledge the role of a structured hydrophobic core, which includes the interface area...
October 18, 2016: International Journal of Molecular Sciences
Yadveer Singh Grewal, Muhammad J A Shiddiky, Stephen M Mahler, Gerard A Cangelosi, Matt Trau
Rapid progress in disease biomarker discovery has increased the need for robust detection technologies. In the past several years, the designs of many immunoaffinity reagents have focused on lowering costs, improving specificity while also promoting stability. Antibody fragments (scFvs) have long been displayed on the surface of yeast and phage libraries for selection, however the stable production of such fragments presents challenges that hamper their widespread use in diagnostics. Membrane and cell wall proteins similarly suffer from stability problems when solubilized from their native environment...
October 20, 2016: ACS Applied Materials & Interfaces
Juexin Wang, Dingding Shen, Geqing Xia, Wangzhen Shen, Robert L Macdonald, Dong Xu, Jing-Qiong Kang
Mutations in GABAA receptor subunit genes are frequently associated with epilepsy, and nonsense mutations in GABRG2 are associated with several epilepsy syndromes including childhood absence epilepsy, generalized tonic clonic seizures and the epileptic encephalopathy, Dravet syndrome. The molecular basis for the phenotypic heterogeneity of mutations is unclear. Here we focused on three nonsense mutations in GABRG2 (GABRG2(R136*), GABRG2(Q390*) and GABRG2(W429*)) associated with epilepsies of different severities...
October 20, 2016: Scientific Reports
Anna A Ye, Stuart Cane, Thomas J Maresca
High-fidelity transmission of the genome through cell division requires that all sister kinetochores bind to dynamic microtubules (MTs) from opposite spindle poles. The application of opposing forces to this bioriented configuration produces tension that stabilizes kinetochore-microtubule (kt-MT) attachments. Defining the magnitude of force that is applied to kinetochores is central to understanding the mechano-molecular underpinnings of chromosome segregation; however, existing kinetochore force measurements span orders of magnitude...
October 20, 2016: Nature Communications
Y Liu, L Huang, H Ye, X Lv
Interferon regulatory factor-7 (IRF-7) is involved in pulmonary infection and pneumonia. Here, a synthetic strategy that combined quantitative structure-activity relationship (QSAR)-based virtual screening and in vitro binding assay was described to identify new and potent mediator ligands of IRF-7 from natural products. In the procedure, a QSAR scoring function was developed and validated using Gaussian process (GP) regression and a structure-based set of protein-ligand affinity data. By integrating hotspot pocket prediction, pharmacokinetics profile analysis and molecular docking calculations, the scoring function was successfully applied to virtual screening against a large library of structurally diverse, drug-like natural products...
October 20, 2016: SAR and QSAR in Environmental Research
K M Saravanan, S Suvaithenamudhan, S Parthasarathy, S Selvaraj
To adopt a particular fold, a protein requires several interactions between its amino acid residues. The energetic contribution of these residue-residue interactions can be approximated by extracting statistical potentials from known high resolution structures. Several methods based on statistical potentials extracted from unrelated proteins are found to make a better prediction of probability of point mutations. We postulate that the statistical potentials extracted from known structures of similar folds with varying sequence identity can be a powerful tool to examine probability of point mutation...
October 19, 2016: Proteins
L Chen, G Guo, X J Yuan, J Zhang, A Y Wen, X H Sun, T Shao
The objective of this study was to determine the effect of ensiling different ratios of whole crop oat to lucerne on fermentation quality, aerobic stability and in vitro digestibility of silage on the Tibetan plateau. Four experimental treatments were produced varying in the ratio of forages on a fresh matter (FM) basis: 1) 100% oat (control, dry matter (DM) content: 317 g/kg), 2) 90% oat + 10% lucerne (OL10, DM content: 316 g/kg), 3) 80% oat+ 20% lucerne (OL20, DM content: 317 g/kg) and 4) 70% oat+ 30% lucerne (OL30, DM content: 318 g/kg)...
October 20, 2016: Journal of Animal Physiology and Animal Nutrition
Simona Citro, Susanna Chiocca
Attachment of ubiquitin or ubiquitin-like (Ubl) modifiers, such as the small ubiquitin-related modifier SUMO, is a posttranslational modification (PTM) that reversibly regulates the function and the stability of target proteins. The SUMO paralogs SUMO1 and SUMO2/3, although sharing a common conjugation pathway, seem to play different roles in the cell. Many regulatory mechanisms, which contribute to SUMO-paralog-specific modification, have emerged. We have recently found that cell environment affects SUMO-paralog-specific sumoylation of HDAC1, whose conjugation to SUMO1 and not to SUMO2 facilitates its protein turnover...
2017: Methods in Molecular Biology
Darren M Hutt, Daniela Martino Roth, Christelle Marchal, Marion Bouchecareilh
Gene expression is regulated in part through the reversible acetylation of histones, by the action of histone acetyltransferases (HAT) and histone deacetylases (HDAC). HAT activity results in the addition of acetyl groups on the lysine residues of histone tails leading to decondensation of the chromatin, and increased gene transcription in general, whereas HDACs remove these acetyl groups, thus leading to an overall suppression of gene transcription. Recent evidence has elucidated that histones are not the only components of the proteome that are targeted by HATs and HDACs...
2017: Methods in Molecular Biology
Yu-Chao Zuo, Hong-Lian Li, Nan-Xiang Xiong, Jian-Ying Shen, Yi-Zhi Huang, Peng Fu, Hong-Yang Zhao
Nogo-66 plays a central role in the myelin-mediated inhibition of neurite outgrowth. Tau is a microtubule-associated protein involved in microtubule assembly and stabilization. It remains unverified whether tau interacts directly with growth factor receptors, or engages in cross-talk with regeneration inhibitors like Nogo-66. Here, we report that plasmid overexpression of tau significantly elevated the protein levels of total tau, phosphorylated tau, and microtubule-affinity regulating kinase (MARK). Nogo-66 transiently elevated the total tau protein level and persistently reduced the level of p-S262 tau (tau phosphorylated at serine 262), whereas it had little influence on the level of p-T205 tau (tau phosphorylated at threonine 205)...
October 19, 2016: Neuroscience Bulletin
Alberto Campanaro, Raffaella Battaglia, Massimo Galbiati, Ari Sadanandom, Chiara Tonelli, Lucio Conti
SUMOylation and anther growth. During fertilization, stamen elongation needs to be synchronized with pistil growth. The phytohormone gibberellic acid (GA) promotes stamen growth by stimulating the degradation of growth repressing DELLA proteins. DELLA accumulation is negatively regulated by GAs through the ubiquitin-proteasome system. In Arabidopsis thaliana, a proportion of DELLAs is also conjugated to the small ubiquitin-like modifier (SUMO) protein, which stabilizes DELLAs. Increased DELLA levels occur in the SUMO protease-deficient OVERLY TOLERANT TO SALT 1 and 2 (ots1 ots2) double mutants, especially under salt stress conditions...
October 19, 2016: Plant Reproduction
James C Campbell, Alexander Tischer, Venkata Machha, Laurie Moon-Tasson, Banumathi Sankaran, Choel Kim, Matthew Auton
von Willebrand factor׳s (VWF) primary hemostatic responsibility is to deposit platelets at sites of vascular injury to prevent bleeding. This function is mediated by the interaction between the VWF A1 domain and the constitutively active platelet receptor, GPIbα. The crystal structure of the A1 domain harboring the von Willebrand disease (vWD) type 2M mutation p.Gly1324Ser has been recently published in the Journal of Biological Chemistry describing its effect on the function and structural stability of the A1 domain of VWF, "Mutational constraints on local unfolding inhibit the rheological adaptation of von Willebrand factor" [1]...
June 2016: Data in Brief
Jorge L Rosas-Trigueros
Bax is a protein that promotes apoptosis (a form of cell death). The atomistic details of the mechanism by which Bax is activated during apoptosis remain a subject of debate. C-terminal basic residues in the sequence of Bax show remarkable conservation across a variety of species. The role of these charged residues in the stability of Bax was investigated by submitting substituted mutants to molecular dynamics simulations at high temperatures. Mutation of either or both K189 and K190 led to dramatic changes in helical content, radius of gyration, proximity of the C terminus to the core of the protein, exposure of the BH3 domain, and bundling of the core...
October 2016: FEBS Open Bio
Patricia Müller-Moulé, Kazunari Nozue, Melissa L Pytlak, Christine M Palmer, Michael F Covington, Andreah D Wallace, Stacey L Harmer, Julin N Maloof
Plants respond to neighbor shade by increasing stem and petiole elongation. Shade, sensed by phytochrome photoreceptors, causes stabilization of PHYTOCHROME INTERACTING FACTOR proteins and subsequent induction of YUCCA auxin biosynthetic genes. To investigate the role of YUCCA genes in phytochrome-mediated elongation, we examined auxin signaling kinetics after an end-of-day far-red (EOD-FR) light treatment, and found that an auxin responsive reporter is rapidly induced within 2 hours of far-red exposure. YUCCA2, 5, 8, and 9 are all induced with similar kinetics suggesting that they could act redundantly to control shade-mediated elongation...
2016: PeerJ
Oselyne T W Ong, Lauren J Young, Julie M Old
BACKGROUND: Reference genes serve an important role as an endogenous control/standard for data normalisation in gene expression studies. Although reference genes have recently been suggested for marsupials, independent analysis of reference genes on different immune tissues is yet to be tested. Therefore, an assessment of reference genes is needed for the selection of stable, expressed genes across different marsupial tissues. METHODS: The study was conducted on red-tailed phascogales (Phascogale calura) using five juvenile and five adult males...
2016: PeerJ
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