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https://www.readbyqxmd.com/read/29224116/chemical-shift-assignments-of-the-partially-deuterated-fyn-sh2-sh3-domain
#1
Fabien Kieken, Karine Loth, Nico van Nuland, Peter Tompa, Tom Lenaerts
Src Homology 2 and 3 (SH2 and SH3) are two key protein interaction modules involved in regulating the activity of many proteins such as tyrosine kinases and phosphatases by respective recognition of phosphotyrosine and proline-rich regions. In the Src family kinases, the inactive state of the protein is the direct result of the interaction of the SH2 and the SH3 domain with intra-molecular regions, leading to a closed structure incompetent with substrate modification. Here, we report the 1H, 15N and 13C backbone- and side-chain chemical shift assignments of the partially deuterated Fyn SH3-SH2 domain and structural differences between tandem and single domains...
December 9, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/29218600/the-sh3-binding-domain-of-cx43-participates-in-loop-tail-interactions-critical-for-cx43-hemichannel-activity
#2
Jegan Iyyathurai, Nan Wang, Catheleyne D'hondt, Jean X Jiang, Luc Leybaert, Geert Bultynck
Connexin 43 (Cx43) hemichannels establish local signaling networks via the release of ATP and other molecules, but their excessive opening may result in cell death. Hence, the activity of Cx43-hemichannels ought to be critically controlled. This involves interactions between the C-terminal tail (CT) and the cytoplasmic loop (CL), more particularly the L2 domain within CL. Previous work revealed an important role for the last nine amino acids of the Cx43 CT by targeting the L2 domain, as these nine amino acids were sufficient to restore the activity of CT-truncated Cx43-hemichannels...
December 7, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29215114/concentration-dependent-binding-of-cdse-quantum-dots-on-the-sh3-domain
#3
David R Bell, Seung-Gu Kang, Tien Huynh, Ruhong Zhou
Quantum dots (QDs) are being used increasingly in applications for solar panels, consumer electronics, and biomedical imaging. For biomedical applications, QDs are typically coated with a biocompatible molecule for the system of interest. Experiments have indicated a QD dose-dependent and surface coating-dependent toxicity, with a portion of the toxicity being ascribed to interference with biomolecules. In this work, the interaction of trioctylphosphine oxide (TOPO) coated (CdSe)13 QDs with the SRC homology 3 domain (SH3) protein domain are explored using molecular dynamics simulations...
December 7, 2017: Nanoscale
https://www.readbyqxmd.com/read/29212769/functional-and-structural-characterization-of-a-novel-malignant-hyperthermia-susceptible-variant-of-dhpr-%C3%AE-1a-subunit-cacnb1
#4
Claudio F Perez, Jose M Eltit, Jose R Lopez, Dóra Bodnár, Angela F Dulhunty, Shouvik Aditya, Marco G Casarotto
Malignant Hyperthermia (MH) susceptibility has been recently linked to a novel variant of β1a subunit of the dihydropyridine receptor (DHPR), a channel essential for Ca2+ regulation in skeletal muscle. Here we evaluate the effect of the mutant variant V156A on the structure/function of DHPR β1a subunit and assess its role on Ca2+ metabolism of cultured myotubes. Using differential scanning fluorimetry we show that mutation V156A causes a significant reduction in thermal stability of the Src homology 3 (SH3)/Guanylate Kinase (GK) core domain of β1a subunit...
December 6, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29208460/ralgps2-is-involved-in-tunneling-nanotubes-formation-in-5637-bladder-cancer-cells
#5
A D'Aloia, G Berruti, B Costa, C Schiller, R Ambrosini, V Pastori, E Martegani, M Ceriani
RalGPS2 is a Ras-independent Guanine Nucleotide Exchange Factor (GEF) for RalA containing a PH domain and an SH3-bindind region and it is involved in several cellular processes, such as cytokinesis, control of cell cycle progression, differentiation, cytoskeleton organization and rearrangement. Up to now, few data have been published regarding RalGPS2 role in cancer cells, and its involvement in bladder cancer is yet to be established. In this paper we demonstrated that RalGPS2 is expressed in urothelial carcinoma-derived 5637 cancer cells and is essential for cellular growth...
December 2, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29206845/turbulence-in-protein-folding-vorticity-scaling-and-diffusion-of-probability-flows
#6
Vladimir A Andryushchenko, Sergei F Chekmarev
Recently, when studying folding of a SH3 domain, we discovered that the flows of transitions between protein states can be surprisingly similar to turbulent fluid flows. This similarity was not restricted by a vortex pattern of the flow fields but extended to a spatial correlation of flow fluctuations, resulting, in particular, in the structure functions such as in the Kolmogorov theory of homogeneous and isotropic turbulence. Here, we undertake a detailed analysis of spatial distribution of folding flows and their similarity to turbulent fluid flows...
2017: PloS One
https://www.readbyqxmd.com/read/29199069/vglut1-binding-to-endophilin-or-intersectin1-and-dynamin-phosphorylation-in-a-diurnal-context
#7
Karin Richter, Isabelle Schmutz, Mahesh Darna, Johannes-F Zander, Rohit Chavan, Urs Albrecht, Gudrun Ahnert-Hilger
Glutamate is concentrated into synaptic vesicles (SV) by the vesicular glutamate transporters (VGLUT) 1and 2. VGLUTs also harbour a Na+/Pi -transport activity when residing at the plasma membrane. Here we aimed to identify whether the diurnal switches of VGLUT1 parallels interactions with or modification of endocytic proteins VGLUT1 and dynamin bind to SH3 domains of either endophilin (Enph) or intersectin 1 (ITSN1) harbouring one or five SH3 domains A-E, respectively. We followed diurnal variations by pull down experiments using SH3 fusion protein and brains from mice entrained in a strict 24 h light dark cycle (12 h light Zeitgeber (ZT) 0, 6; 12 h dark ZT 12 and 18)...
November 30, 2017: Neuroscience
https://www.readbyqxmd.com/read/29185419/activation-of-discs-large-by-apkc-aligns-the-mitotic-spindle-to-the-polarity-axis-during-asymmetric-cell-division
#8
Ognjen Golub, Brett Wee, Rhonda A Newman, Nicole M Paterson, Kenneth E Prehoda
Asymmetric division generates cellular diversity by producing daughter cells with different fates. In animals, the mitotic spindle aligns with Par complex polarized fate determinants, ensuring that fate determinant cortical domains are bisected by the cleavage furrow. Here, we investigate the mechanisms that couple spindle orientation to polarity during asymmetric cell division of Drosophila neuroblasts. We find that the tumor suppressor Discs large (Dlg) links the Par complex component atypical Protein Kinase C (aPKC) to the essential spindle orientation factor GukHolder (GukH)...
November 29, 2017: ELife
https://www.readbyqxmd.com/read/29175910/fam83g-paws1-controls-cytoskeletal-dynamics-and-cell-migration-through-association-with-the-sh3-adaptor-cd2ap
#9
Timothy D Cummins, Kevin Z L Wu, Polyxeni Bozatzi, Kevin S Dingwell, Thomas J Macartney, Nicola T Wood, Joby Varghese, Robert Gourlay, David G Campbell, Alan Prescott, Eric Griffis, James C Smith, Gopal P Sapkota
Our previous studies of PAWS1 (Protein Associated With SMAD1) have suggested that this molecule has roles beyond BMP signalling. To investigate these roles, we have used CRISPR/Cas9 to generate PAWS1 knockout U2OS osteosarcoma cells. Here, we show that PAWS1 plays a role in the regulation of the cytoskeletal machinery, including actin and focal adhesion dynamics, and cell migration. Confocal microscopy and live cell imaging of actin in U2OS cells indicate that PAWS1 is also involved in cytoskeletal dynamics and organization...
November 24, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29173143/the-role-of-grb2-in-cancer-and-peptides-as-grb2-antagonists
#10
Muhammad Ijaz, Muhammad Shahbaz, Wenjie Jiang, Abdel Hamid Fathy, Effat Un Nesa, Wang Feng Shan
Growth factor receptor-bound protein 2 (Grb2) is a 25 kDa adaptor protein, which was originally discovered to accomplish basic cellular events such as cell growth, cell proliferation, and metabolism. However, recent studies evidenced that Grb2 was largely involved in multiple tumor malignancies. The mature Grb2 is a 217 amino acid sequence, which consists of one Src homology 2 (SH2) domain flanked by two Src homology 3 (SH3) domains. Using these binding motives, the ubiquitously expressed Grb2 acts as an intermediate between cell-surface activated receptors and downstream targets...
November 23, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/29170974/comparative-proteomic-analysis-of-amnion-membrane-transplantation-and-cross-linking-treatments-in-an-experimental-alkali-injury-model
#11
Sevgi Subasi, Ozgul Altintas, Murat Kasap, Nil Guzel, Gurler Akpinar, Suleyman Karaman
PURPOSE: In this study, by using a two-dimensional (2D) electrophoresis-based experimental approach, we aimed at understanding the nature of alkali injuries and the underlying mechanisms. A secondary aim was to compare the effects of cross-linking (CXL) and amnion membrane transplantation (AMT) on corneal protein compositions at the end of the early repair phase after injured with alkali. METHOD: The right corneas of 24 rabbits were injured with a 1 N solution of NaOH...
November 23, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/29158086/pfn2a-a-new-partner-of-rar%C3%AE-in-the-cytoplasm
#12
Dina Andriamoratsiresy, Aleksandr Piskunov, Regis Lutzing, Cécile Rochette-Egly
Retinoic acid receptors (RARs) are classically considered as nuclear ligand-dependent regulators of transcription. Here we highlighted a novel face of the RARα subtype: RARα is present in low amounts in the cytoplasm of mouse embryonic fibroblasts (MEFs) where it interacts with profilin2a (PFN2A), a small actin-binding protein involved in filaments polymerisation. The interaction involves the N-terminal proline-rich motif (PRM) of RARα and the SH3-like domain of PFN2a. When increased in the cytoplasm, RARα competes with other PFN2a-binding proteins bearing PRMs and involved in actin filaments elongation...
November 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29138807/role-of-lasp-1-a-novel-sox9-transcriptional-target-in-the-progression-of-lung-cancer
#13
Jianguang Shi, Jing Guo, Xinjian Li
Lung cancer accounts for most cancer-related deaths worldwide. However, the underlying mechanism by which it mediates the progression of lung cancer remains unclear. Expression of LASP-1 (LIM and SH3 protein 1) was evaluated in lung cancer tissues and tumor-adjacent normal tissues using immunohistochemistry and western blotting. Functional studies have shown that siRNA-mediated silencing of LASP-1 in human lung cancer cells and reduced cell proliferation, migration, and invasion. Flow cytometry and immunofluorescence staining also revealed that rate of cell apoptosis was increased after knockdown of expression of LASP-1, thereby suggesting that LASP-1 may function as an oncogene during lung cancer progression...
November 10, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29138001/pdz-ligand-binding-induced-conformational-coupling-of-the-pdz-sh3-gk-tandems-in-psd-95-family-maguks
#14
Menglong Zeng, Fei Ye, Jia Xu, Mingjie Zhang
DLG MAGUKs are abundantly expressed in glutamatergic synapses, crucial for synaptic transmission and plasticity by anchoring various postsynaptic components including glutamate receptors, downstream scaffold proteins and signaling enzymes. Different DLG members have shared structures and functions, but also contain unique features. How DLG family proteins function individually and cooperatively are largely unknown. Here, we report that PSD-95 PDZ3 directly couples with SH3-GK tandem in a PDZ ligand binding-dependent manner, and the coupling can promote PSD-95 dimerization and multimerization...
November 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29137268/understanding-the-mechanism-of-binding-between-gab2-and-the-c-terminal-sh3-domain-from-grb2
#15
Angelo Toto, Daniela Bonetti, Alfonso De Simone, Stefano Gianni
Gab2 is a large disordered protein that regulates several cellular signalling pathways and is overexpressed in different forms of cancer. Because of its disordered nature, a detailed characterization of the mechanisms of recognition between Gab2 and its physiological partners is particularly difficult. Here we provide a detailed kinetic characterization of the binding reaction between Gab2 and the C-terminal SH3 domain of the growth factor receptor-bound protein 2 (Grb2). We demonstrate that Gab2 folds upon binding following an induced fit type mechanism, whereby recognition is characterized by the formation of an intermediate, in which Gab2 is primarily disordered...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29130122/arhgef9-mutations-in-epileptic-encephalopathy-intellectual-disability-toward-understanding-the-mechanism-underlying-phenotypic-variation
#16
Jing-Yang Wang, Peng Zhou, Jie Wang, Bin Tang, Tao Su, Xiao-Rong Liu, Bing-Mei Li, Heng Meng, Yi-Wu Shi, Yong-Hong Yi, Na He, Wei-Ping Liao
ARHGEF9 resides on Xq11.1 and encodes collybistin, which is crucial in gephyrin clustering and GABAA receptor localization. ARHGEF9 mutations have been identified in patients with heterogeneous phenotypes, including epilepsy of variable severity and intellectual disability. However, the mechanism underlying phenotype variation is unknown. Using next-generation sequencing, we identified a novel mutation, c.868C > T/p.R290C, which co-segregated with epileptic encephalopathy, and validated its association with epileptic encephalopathy...
November 13, 2017: Neurogenetics
https://www.readbyqxmd.com/read/29121345/early-postnatal-exposure-to-airborne-fine-particulate-matter-induces-autism-like-phenotypes-in-male-rats
#17
Kang Li, Li Li, Bo Cui, Zhihui Gai, Qiuyue Li, Shumei Wang, Jun Yan, Bencheng Lin, Lei Tian, Huanliang Liu, Xiaohua Liu, Zhuge Xi
Epidemiological studies have revealed that ambient fine particulate matter (PM2.5) exposure is closely associated with autism spectrum disorder (ASD). However, there is a relative paucity of laboratory data to support this epidemic finding. In order to assess the relationship between PM2.5 exposure and ASD, neonatal male Sprague-Dawley (SD) rats were chosen and exposed to PM2.5 (2 or 20 mg/kg body weight, once a day) by intranasal instillation from postnatal day (PND) 8 to 22. It was found that when exposed to PM2...
November 7, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29097383/mind-the-sr-gap-roles-of-slit-robo-gaps-in-neurons-brains-and-beyond
#18
REVIEW
Bethany Lucas, Jeff Hardin
The Slit-Robo GTPase-activating proteins (srGAPs) were first identified as potential Slit-Robo effectors that influence growth cone guidance. Given their N-terminal F-BAR, central GAP and C-terminal SH3 domains, srGAPs have the potential to affect membrane dynamics, Rho family GTPase activity and other binding partners. Recent research has clarified how srGAP family members act in distinct ways at the cell membrane, and has expanded our understanding of the roles of srGAPs in neuronal and non-neuronal cells...
November 2, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29096051/identification-and-initial-characterization-of-novel-neural-immediate-early-genes-possibly-differentially-contributing-to-foraging-related-learning-and-memory-processes-in-the-honeybee
#19
A Ugajin, H Uchiyama, T Miyata, T Sasaki, S Yajima, M Ono
Despite possessing a limited number of neurones compared to vertebrates, honeybees show remarkable learning and memory performance, an example being 'dance communication'. In this phenomenon, foraging honeybees learn the location of a newly discovered food source and transmit the information to nestmates by symbolic abdomen vibrating behaviour, leading to navigation of nestmates to the new food source. As an initial step toward understanding the detailed molecular mechanisms underlying the sophisticated learning and memory performance of the honeybee, we focused on the neural immediate early genes (IEGs), which are specific genes quickly transcribed after neural activity without de novo protein synthesis...
November 2, 2017: Insect Molecular Biology
https://www.readbyqxmd.com/read/29078335/structural-insights-into-binding-of-stac-proteins-to-voltage-gated-calcium-channels
#20
Siobhan M Wong King Yuen, Marta Campiglio, Ching-Chieh Tung, Bernhard E Flucher, Filip Van Petegem
Excitation-contraction (EC) coupling in skeletal muscle requires functional and mechanical coupling between L-type voltage-gated calcium channels (CaV1.1) and the ryanodine receptor (RyR1). Recently, STAC3 was identified as an essential protein for EC coupling and is part of a group of three proteins that can bind and modulate L-type voltage-gated calcium channels. Here, we report crystal structures of tandem-SH3 domains of different STAC isoforms up to 1.2-Å resolution. These form a rigid interaction through a conserved interdomain interface...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
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