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Protein domains

Carlos M Guardia, Raffaella De Pace, Rafael Mattera, Juan S Bonifacino
Selective transport of transmembrane proteins to different intracellular compartments often involves the recognition of sorting signals in the cytosolic domains of the proteins by components of membrane coats. Some of these coats have as their key components a family of heterotetrameric adaptor protein (AP) complexes named AP-1 through AP-5. AP complexes play important roles in all cells, but their functions are most critical in neurons because of the extreme compartmental complexity of these cells. Accordingly, various diseases caused by mutations in AP subunit genes exhibit a range of neurological abnormalities as their most salient features...
March 17, 2018: Current Opinion in Neurobiology
Jeffrey K Holden, Christian N Cunningham
The Hippo pathway is a critical transcriptional signaling pathway that regulates cell growth, proliferation and organ development. The transcriptional enhanced associate domain (TEAD) protein family consists of four paralogous transcription factors that function to modulate gene expression in response to the Hippo signaling pathway. Transcriptional activation of these proteins occurs upon binding to the co-activator YAP/TAZ whose entry into the nucleus is regulated by Lats1/2 kinase. In recent years, it has become apparent that the dysregulation and/or overexpression of Hippo pathway effectors is implicated in a wide range of cancers, including prostate, gastric and liver cancer...
March 20, 2018: Cancers
Takahiro Maekawa, Riki Ogasawara, Arata Tsutaki, Kihyuk Lee, Satoshi Nakada, Koichi Nakazato, Naokata Ishii
High-intensity exercise has recently been shown to cause an increase in brain-derived neurotropic factor (BDNF) in the hippocampus. Some studies have suggested that myokines secreted from contracting skeletal muscle, such as irisin (one of the truncated form of fibronectin type III domain-containing protein 5 (FNDC5)), play important roles in this process. Thus, we hypothesized that locally evoked muscle contractions may cause an increase of BDNF in the hippocampus through some afferent mechanisms. Under anesthesia, Sprague-Dawley rats were fixed on a custom-made dynamometer and their triceps surae muscles were made to maximally contract via delivery of electric stimulations of the sciatic nerve (100 Hz with 1-ms pulse and 3-s duration)...
March 20, 2018: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
Yinfang Wang, Yitong Huang, Youbin Liu, Jinping Li, Yilong Hao, Peihao Yin, Zongjun Liu, Jingzhou Chen, Ying Wang, Nanping Wang, Peng Zhang
Mitochondria are dynamic organelles that are able to change their morphology and cellular distribution by either fission or fusion. However, the molecular mechanisms controlling mitochondrial dynamics in vascular endothelial cells (ECs) remain largely unknown. In this study, we observed that knock down of microtubule-associated tumor suppressor 1 (MTUS1) in ECs inhibited tube formation and migration, accompanied with decreased promigratory signalings. We showed that MTUS1 was localized in the outer membrane of mitochondria in ECs...
March 20, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Junghyun L Suh, Brian Watts, Jacob I Stuckey, Jacqueline L Norris-Drouin, Stephanie H Cholensky, Bradley M Dickson, Yi An, Sebastian Mathea, Eidarus Salah, Stefan Knapp, Abid Khan, Alexander T Adams, Brian D Strahl, Cari A Sagum, Mark T Bedford, Lindsey I James, Dmitri B Kireev, Stephen V Frye
Multivalent binding is an efficient means to enhance the affinity and specificity of chemical probes targeting multi-domain proteins in order to study their function and role in disease. While the theory of multivalent binding is straightforward, physical and structural characterization of bivalent binding encounters multiple technical difficulties. We present a case study where a combination of experimental techniques and computational simulations was used to comprehensively characterize the binding and structure-affinity relationships for a series of Bromosporine-based bivalent bromodomain ligands with a bivalent protein, Transcription Initiation Factor TFIID subunit 1 (TAF1)...
March 20, 2018: Biochemistry
A M Vaira, H S Lim, G Bauchan, C J Gulbronson, L Miozzi, N Vinals, A Natilla, J Hammond
The Lolium latent virus (LoLV) major coat protein sequence contains a typical chloroplast transit peptide (cTP) domain. In infected Nicotiana benthamiana leaf tissue, LoLV coat proteins can be detected at the chloroplast. In transient expression, several N-terminal deletions of the CP sequence, increasing in length, result in disruption of the domain functionality, markedly affecting intracellular localization. A yeast two-hybrid-based study using LoLV CP as bait identified several potentially interacting Arabidopsis host proteins, most of them with chloroplast-linked pathways...
March 20, 2018: Journal of General Virology
Rajendra-Prasad Janapatla, Chyi-Liang Chen, Mei-Hua Hsu, Wan-Ting Liao, Cheng-Hsun Chiu
PURPOSE: Pneumococcal virulence protein-based vaccines can provide serotype-independent protection against pneumococcal infections. Many studies, including clinical observational studies on Thomsen-Friedenrich antigen exposure and haemolytic uremic syndrome, defined the role of neuraminidases NanA, NanB and NanC in host-pneumococcus interaction. Since neuraminidases are major virulence proteins, they are potential targets for both vaccines and small molecule inhibitors. Here we explored the utility of three neuraminidases as protein vaccine antigens to generate neutralizing antibodies and to increase survival following pneumococcal infections...
March 20, 2018: Journal of Medical Microbiology
Tanuj Sharma, Mohammad Imran Siddiqi
Unique intrinsic properties of peptides like low toxicity, high biological activity and specificity make them attractive therapeutic agents. PDZ binding peptide inhibitors have been demonstrated for curing of Alzheimer, Parkinson, Dementia and other central nervous system ailments. In this article, we report the successful use of an integrated computational protocol to analyze the structural basis of how peptides bind to the shallow groove of the third PDZ domain (PDZ3) from the Post Synaptic Density (PSD-95) protein...
March 20, 2018: Journal of Biomolecular Structure & Dynamics
Daniel Lüdke, Charlotte Roth, Denise Hartken, Marcel Wiermer
The Arabidopsis nuclear transport receptor IMPORTIN-α3/MOS6 (MODIFIER OF SNC1, 6) is required for constitutive defense responses of the auto-immune mutant snc1 (suppressor of npr1-1, constitutive 1) and contributes to basal disease resistance, suggesting a role in nuclear import of defense-regulatory cargo proteins. We recently showed that MOS6 selectively interacts with TN13, a TIR-NBS protein involved in basal resistance to Pseudomonas syringae pv. tomato (Pst) DC3000 lacking the effectors AvrPto and AvrPtoB...
March 20, 2018: Plant Signaling & Behavior
Ruoxing Lei, Jessica P Lee, Matthew B Francis, Sanjay Kumar
Intrinsically disordered proteins (IDPs) play central roles in numerous cellular processes. While IDP structure and function are often regulated by multisite phosphorylation, the biophysical mechanisms linking these post-translational modifications to IDP structure remain elusive. For example, the intrinsically disordered C-terminal sidearm domain of the neurofilament heavy subunit (NFH-SA) forms a dense brush along axonal NF backbones and is subject to extensive serine phosphorylation. Yet, biophysical insight into the relationship between phosphorylation and structure has been limited by the lack of paradigms in which NF brush conformational responses can be measured in the setting of controlled phosphorylation...
March 20, 2018: Biochemistry
Jian-An Li, Chang-Fu Zhao, Shao-Jun Li, Jun Zhang, Zhen-Hua Li, Qiao Zhang, Xiao-Yu Yang, Chun-Fang Zan
Insulin-like growth factor 1 (IGF-1) is a potential nutrient for nerve repair. However, it is impractical as a therapy because of its limited half-life, rapid clearance, and limited target specificity. To achieve targeted and long-lasting treatment, we investigated the addition of a binding structure by fusing a collagen-binding domain to IGF-1. After confirming its affinity for collagen, the biological activity of this construct was examined by measuring cell proliferation after transfection into PC12 and Schwann cells using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay...
February 2018: Neural Regeneration Research
Geetha Rani Yuvaraj, Baddrireddi Subhadra Lakshmi
Estrogen receptor α (ER α) is an important therapeutic target in the regulation of ligand dependent signaling in breast cancer. The current study investigates the anti-estrogenic potential of the Diarylheptanoid, 5-hydroxy-7-(4-hydroxy-3 methoxyphenyl)-1-phenyl-3-heptanone (DAH) in silico. Rigid Docking analysis of DAH at the ligand binding domain (LBD) of ER α showed hydrogen bond interactions with Arg394 and Glu353 at the active site, similar to the positive controls 4 - Hydroxy Tamoxifen (4-OHT) and Fulvestrant (FUL)...
March 20, 2018: Journal of Biomolecular Structure & Dynamics
Dejian Zhou, Xing Zhu, Sanduo Zheng, Dan Tan, Meng-Qiu Dong, Keqiong Ye
Assembly of eukaryotic ribosome is a complicated and dynamic process that involves a series of intermediates. It is unknown how the highly intertwined structure of 60S large ribosomal subunits is established. Here, we report the structure of an early nucleolar pre-60S ribosome determined by cryo-electron microscopy at 3.7 Å resolution, revealing a half-assembled subunit. Domains I, II and VI of 25S/5.8S rRNA pack tightly into a native-like substructure, but domains III, IV and V are not assembled. The structure contains 12 assembly factors and 19 ribosomal proteins, many of which are required for early processing of large subunit rRNA...
March 19, 2018: Protein & Cell
Olesya Yu Shoeva
The wheat TaMyc1 gene encodes for transcriptional factor (TF) with bHLH domain. The gene is expressed in purple wheat grains and activates transcription of the anthocyanin biosynthesis structural genes. To reveal the features of TaMyc1 regulation in wheat pericarp transcription start sites (TSS) were identified by 5' RACE mean and translation efficiency was predicted by in silico methods. Three alternative transcript variants of TaMyc1 differing by 5' leader sequence only were identified in purple pericarp...
March 19, 2018: Molecular Biology Reports
Xiabin Chen, Jing Deng, Wenpeng Cui, Shurong Hou, Jinling Zhang, Xirong Zheng, Xin Ding, Huimei Wei, Ziyuan Zhou, Kyungbo Kim, Chang-Guo Zhan, Fang Zheng
Cocaine abuse is a worldwide public health and social problem without a US Food and Drug Administration (FDA)-approved medication. Accelerating cocaine metabolism that produces biologically inactive metabolites by administration of an efficient cocaine hydrolase (CocH) has been recognized as a promising strategy for cocaine abuse treatment. However, the therapeutic effects of CocH are limited by its short biological half-life (e.g., 8 h or shorter in rats). In this study, we designed and prepared a set of Fc-fusion proteins constructed by fusing Fc(M3) with CocH3 at the N-terminus of CocH3...
March 19, 2018: AAPS Journal
Ying Huang, Keke Han, Qian Ren
Toll receptors are involved in innate immunity of invertebrates. In this study, we identify and characterize two Toll genes (named HcToll4 and HcToll5 ) from triangle sail mussel Hyriopsis cumingii. HcToll4 has complete cDNA sequence of 3,162 bp and encodes a protein of 909 amino acids. HcToll5 cDNA is 4,501 bp in length and encodes a protein of 924 amino acids. Both deduced HcToll4 and HcToll5 protein contain signal peptide, extracellular leucine rich repeats (LRRs), and intracellular Toll/interleukin-1 (IL-1) receptor domains...
2018: Frontiers in Physiology
Davoud Mozhdehi, Kelli M Luginbuhl, Joseph R Simon, Michael Dzuricky, Rüdiger Berger, H Samet Varol, Fred C Huang, Kristen L Buehne, Nicholas R Mayne, Isaac Weitzhandler, Mischa Bonn, Sapun H Parekh, Ashutosh Chilkoti
Post-translational modification of proteins is a strategy widely used in biological systems. It expands the diversity of the proteome and allows for tailoring of both the function and localization of proteins within cells as well as the material properties of structural proteins and matrices. Despite their ubiquity in biology, with a few exceptions, the potential of post-translational modifications in biomaterials synthesis has remained largely untapped. As a proof of concept to demonstrate the feasibility of creating a genetically encoded biohybrid material through post-translational modification, we report here the generation of a family of three stimulus-responsive hybrid materials-fatty-acid-modified elastin-like polypeptides-using a one-pot recombinant expression and post-translational lipidation methodology...
March 19, 2018: Nature Chemistry
M Charpentier, A H Y Khedher, S Menoret, A Brion, K Lamribet, E Dardillac, C Boix, L Perrouault, L Tesson, S Geny, A De Cian, J M Itier, I Anegon, B Lopez, C Giovannangeli, J P Concordet
In genome editing with CRISPR-Cas9, transgene integration often remains challenging. Here, we present an approach for increasing the efficiency of transgene integration by homology-dependent repair (HDR). CtIP, a key protein in early steps of homologous recombination, is fused to Cas9 and stimulates transgene integration by HDR at the human AAVS1 safe harbor locus. A minimal N-terminal fragment of CtIP, designated HE for HDR enhancer, is sufficient to stimulate HDR and this depends on CDK phosphorylation sites and the multimerization domain essential for CtIP activity in homologous recombination...
March 19, 2018: Nature Communications
Maria A Schumacher, Chris D den Hengst, Matthew J Bush, T B K Le, Ngat T Tran, Govind Chandra, Wenjie Zeng, Brady Travis, Richard G Brennan, Mark J Buttner
Streptomycetes are notable for their complex life cycle and production of most clinically important antibiotics. A key factor that controls entry into development and the onset of antibiotic production is the 68-residue protein, BldC. BldC is a putative DNA-binding protein related to MerR regulators, but lacks coiled-coil dimerization and effector-binding domains characteristic of classical MerR proteins. Hence, the molecular function of the protein has been unclear. Here we show that BldC is indeed a DNA-binding protein and controls a regulon that includes other key developmental regulators...
March 19, 2018: Nature Communications
Soham Sengupta, Rachel Nechushtai, Patricia A Jennings, Jose' N Onuchic, Pamela A Padilla, Rajeev K Azad, Ron Mittler
The iron-sulfur (2Fe-2S) binding motif CDGSH appears in many important plant and animal proteins that regulate iron and reactive oxygen metabolism. In human it is found in CISD1-3 proteins involved in diabetes, obesity, cancer, aging, cardiovascular disease and neurodegeneration. Despite the important biological role of the CDGSH domain, its origin, evolution and diversification, are largely unknown. Here, we report that: (1) the CDGSH domain appeared early in evolution, perhaps linked to the heavy use of iron-sulfur driven metabolism by early organisms; (2) a CISD3-like protein with two CDGSH domains on the same polypeptide appears to represent the ancient archetype of CDGSH proteins; (3) the origin of the human CISD3 protein is linked to the mitochondrial endosymbiotic event; (4) the CISD1/2 type proteins that contain only one CDGSH domain, but function as homodimers, originated after the divergence of bacteria and archaea/eukaryotes from their common ancestor; and (5) the human CISD1 and CISD2 proteins diverged about 650-720 million years ago, and CISD3 and CISD1/2 share their descent from an ancestral CISD about 1-1...
March 19, 2018: Scientific Reports
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