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https://www.readbyqxmd.com/read/28816235/g3bp2-is-involved-in-isoproterenol-induced-cardiac-hypertrophy-through-activating-the-nf-%C3%AE%C2%BAb-signaling-pathway
#1
Hui-Qi Hong, Jing Lu, Xiu-Li Fang, Yu-Hong Zhang, Yi Cai, Jing Yuan, Pei-Qing Liu, Jian-Tao Ye
The RasGAP SH3 domain-binding proteins (G3BPs) are a family of RNA-binding proteins that can co-ordinate signal transduction and post-transcriptional gene regulation. G3BPs have been shown to be involved in mediating a great diversity of cellular processes such as cell survival, growth, proliferation and apoptosis. But the potential roles of G3BPs in the pathogenesis and progression of cardiovascular diseases remain to be clarified. In the present study, we provide the first evidence that suggests the participation of G3BP2 in cardiac hypertrophy...
August 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28813247/switch-like-arp2-3-activation-upon-wasp-and-wip-recruitment-to-an-apparent-threshold-level-by-multivalent-linker-proteins-in-vivo
#2
Yidi Sun, Nicole T Leong, Tommy Jiang, Astou Tangara, Xavier Darzacq, David G Drubin
Actin-related protein 2/3 (Arp2/3) complex activation by nucleation promoting factors (NPFs) such as WASP, plays an important role in many actin-mediated cellular processes. In yeast, Arp2/3-mediated actin filament assembly drives endocytic membrane invagination and vesicle scission. Here we used genetics and quantitative live-cell imaging to probe the mechanisms that concentrate NPFs at endocytic sites, and to investigate how NPFs regulate actin assembly onset. Our results demonstrate that SH3 (Src homology 3) domain-PRM (proline-rich motif) interactions involving multivalent linker proteins play central roles in concentrating NPFs at endocytic sites...
August 16, 2017: ELife
https://www.readbyqxmd.com/read/28808245/structural-characterization-of-cas-sh3-domain-selectivity-and-regulation-reveals-new-cas-interaction-partners
#3
Jakub Gemperle, Rozálie Hexnerová, Martin Lepšík, Petr Tesina, Michal Dibus, Marian Novotný, Jan Brábek, Václav Veverka, Daniel Rosel
CAS is a docking protein downstream of the proto-oncogene Src with a role in invasion and metastasis of cancer cells. The CAS SH3 domain is indispensable for CAS-mediated signaling, but structural aspects of CAS SH3 ligand binding and regulation are not well understood. Here, we identified the consensus CAS SH3 binding motif and structurally characterized the CAS SH3 domain in complex with ligand. We revealed the requirement for an uncommon centrally localized lysine residue at position +2 of CAS SH3 ligands and two rather dissimilar optional anchoring residues, leucine and arginine, at position +5...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28805214/the-low-populated-folding-intermediate-of-a-mutant-of-the-fyn-sh3-domain-identified-by-a-simple-model
#4
Jing Wu, Guojun Chen, Zhuqing Zhang, Ping Zhang, Tao Chen
Experimental studies indicate that the A39V/N53P/V55L Fyn SH3 domain folds from the unfolded state to the native state via a low-populated on-pathway intermediate, whereas the folding of the wildtype is two-state-like. To get insights into the biophysical basis of their different folding mechanisms, we used native-centric models with and without additional transferrable, sequence-dependent nonnative hydrophobic interactions to study the folding behaviors of the Fyn SH3 domain and its mutant. The pure native-centric model predicts that both the wildtype and the mutant fold in a two-state manner, without any detectable intermediate...
August 14, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28799209/computation-guided-design-of-a-stimulus-responsive-multi-enzyme-supramolecular-assembly
#5
Lu Yang, Elliott M Dolan, Sophia K Tan, Tianyun Lin, Eduardo D Sontag, Sagar Khare
The construction of stimulus-responsive supramolecular complexes of metabolic pathway enzymes, inspired by natural multi-enzyme assemblies (metabolons), provides an attractive avenue for efficient and spatio-temporally controllable one-pot biotransformations. We constructed a phosphorylation- and optically-responsive metabolon for the biodegradation of the environmental pollutant 1,2,3-trichloropropane (TCP). The three enzymes in of a synthetic degradation pathway were fused to engineered variants of the peptide-binding domains (SH2, SH3; the latter redesigned to incorporate an unnatural photocrosslinkable amino acid) or their corresponding binding peptides, and enzyme co-localization in response to phosphorylation and UV-light was demonstrated...
August 10, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28790172/postsynaptic-density-95-psd-95-serine-561-phosphorylation-regulates-a-conformational-switch-and-bidirectional-dendritic-spine-structural-plasticity
#6
Qian Wu, Miao Sun, Laura P Bernard, Huaye Zhang
PSD-95 is a major synaptic scaffolding protein that plays a key role in bidirectional synaptic plasticity, which is a process important for learning and memory. It is known that PSD-95 shows increased dynamics upon induction of plasticity. Yet the underlying structural and functional changes in PSD-95 that mediate its role in plasticity remain unclear. Here we show that phosphorylation of PSD-95 at Ser561 in its GK domain, which is mediated by the partitioning defective 1 (Par1) kinases, regulates a conformational switch and is important for bidirectional plasticity...
August 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28777082/crystal-structure-of-the-peg-bound-sh3-domain-of-myosin-ib-from-entamoeba-histolytica-reveals-its-mode-of-ligand-recognition
#7
Gunjan Gautam, Syed Arif Abdul Rehman, Preeti Pandey, Samudrala Gourinath
The versatility in the recognition of various interacting proteins by the SH3 domain drives a variety of cellular functions. Here, the crystal structure of the C-terminal SH3 domain of myosin IB from Entamoeba histolytica (EhMySH3) is reported at a resolution of 1.7 Å in native and PEG-bound states. Comparisons with other structures indicated that the PEG molecules occupy protein-protein interaction pockets similar to those occupied by the peptides in other peptide-bound SH3-domain structures. Also, analysis of the PEG-bound EhMySH3 structure led to the recognition of two additional pockets, apart from the conventional polyproline and specificity pockets, that are important for ligand interaction...
August 1, 2017: Acta Crystallographica. Section D, Structural Biology
https://www.readbyqxmd.com/read/28771359/modulation-of-the-extent-of-cooperative-structural-change-during-protein-folding-by-chemical-denaturant
#8
Prashant N Jethva, Jayant B Udgaonkar
Protein folding and unfolding reactions invariably appear to be highly cooperative reactions, but the structural and sequence determinants of cooperativity are poorly understood. Importantly, it is not known whether cooperative structural change occurs throughout the protein, or whether some parts change cooperatively and other parts change non-cooperatively. In the current study, hydrogen exchange mass spectrometry has been used to show that the mechanism of unfolding of the PI3K SH3 domain is similar in the absence and presence of 5 M urea...
August 3, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28765332/n1-src-kinase-is-required-for-primary-neurogenesis-in-xenopus-tropicalis
#9
Philip A Lewis, Isobel C Bradley, Alastair R Pizzey, Harry V Isaacs, Gareth J O Evans
The presence of the neuronal-specific N1-Src splice variant of the C-Src tyrosine kinase is conserved through vertebrate evolution, suggesting an important role in complex nervous systems. Alternative splicing involving a N1-Src specific microexon leads to a five or six amino acid insertion into the SH3 domain of Src. A prevailing model suggests that N1-Src regulates neuronal differentiation via cytoskeletal dynamics in the growth cone. Here we have investigated the role of n1-src in the early development of the amphibian Xenopus tropicalis, and find that n1-src expression is regulated in embryogenesis, with highest levels detected during the phases of primary and secondary neurogenesis...
August 1, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28755480/g3bp1-interacts-directly-with-the-fmdv-ires-and-negatively-regulates-translation
#10
Alfonso Galan, Gloria Lozano, David Piñeiro, Encarnacion Martinez-Salas
RNA-protein interactions play a pivotal role in the function of picornavirus internal ribosome entry site (IRES) elements. Here we analysed the impact of Ras GTPase SH3 domain binding protein 1 (G3BP1) in the IRES activity of foot-and-mouth disease virus (FMDV). We found that G3BP1 interacts directly with three distinct sequences of the IRES element using RNA electrophoretic mobility-shift assays. Analysis of the interaction with domain 5 indicated that the G3BP1 binding-site is placed at the single-stranded region although it allows large sequence heterogeneity and the hairpin located upstream of this region enhances retarded complex formation...
July 29, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28755476/regulation-of-the-interaction-between-the-neuronal-bin1-isoform-1-and-tau-proteins-role-of-the-sh3-domain
#11
Idir Malki, François-Xavier Cantrelle, Yoann Sottejeau, Guy Lippens, Jean-Charles Lambert, Isabelle Landrieu
Bridging integrator 1 bin1 gene is a genetic determinant of Alzheimer's disease and has been reported to modulate Alzheimer's pathogenesis through pathway(s) involving Tau. The functional impact of Tau/BIN1 interaction as well as the molecular details of this interaction are still not fully resolved. As a consequence, how BIN1 through its interaction with Tau affects Alzheimer's disease risk is also still not determined. To progress in this understanding, interaction of Tau with two BIN1 isoforms was investigated using Nuclear Magnetic Resonance spectroscopy...
July 29, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28754059/disrupting-the-intramolecular-interaction-between-proto-oncogene-c-src-sh3-domain-and-its-self-binding-peptide-ppii-with-rationally-designed-peptide-ligands
#12
Peng Zhou, Shasha Hou, Zhengya Bai, Zhongyan Li, Heyi Wang, Zheng Chen, Yang Meng
Proto-oncogene non-receptor tyrosine protein kinase c-Src has been involved in the development, progression and metastasis of a variety of human cancers. This protein contains two self-binding peptide (SBP) sites separately between the SH3 domain and polyproline-II (PPII) helix and between the SH2 domain and C-terminal phosphorylatable tail (CTPT), which are potential targets of anticancer drugs to regulate the kinase activity. Here, we described an integrated protocol to systematically investigate the structural basis, energetic property and dynamics behaviour of PPII binding to SH3, and to rationally design potent peptide ligands to target the SBP site of SH3-PPII interaction...
July 28, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28751624/understanding-the-mechanism-of-binding-between-gab2-and-the-c-terminal-sh3-domain-from-grb2
#13
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...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28743627/characterization-of-a-novel-non-receptor-tyrosine-kinase-src-from-litopenaeus-vannamei-and-its-response-to-white-spot-syndrome-virus-infection
#14
Defu Yao, Lingwei Ruan, Jingxiang Xu, Hong Shi, Xun Xu
Src family kinases (SFKs), a class of non-receptor tyrosine kinases, mediate a wide aspect of cellular signaling pathways that regulate cell proliferation, differentiation, motility and survival. In this study, we identified and characterized for the first time a novel SFK homologue from Litopenaeus vannamei (designated as LvSrc). Sequence analysis showed that LvSrc had a high homology with the identified SFKs, especially those from invertebrates. LvSrc contained the conserved SH3, SH2 and tyrosine kinase domains, as well as the potential phosphorylation and lipid modification sites...
July 23, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28730474/allosteric-modulation-of-src-family-kinases-with-atp-competitive-inhibitors
#15
Ames C Register, Sujata Chakraborty, Dustin J Maly
The Src family kinases (SFKs) are an important family of tyrosine kinases that are allosterically regulated by their SH2 and SH3 domains. Engagement of SFK SH2 and SH3 domains with their intramolecular ligands leads to reduced kinase activity by stabilizing an inactive ATP-binding site conformation. Disruption of these intramolecular interactions stabilizes a more active ATP-binding site conformation and restores SFK activity. Interestingly, this allosteric relationship is bidirectional in that ATP-competitive ligands that stabilize distinct active site conformations can divergently modulate the abilities of the regulatory SH2 and SH3 domains to participate in intermolecular interactions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28720784/snap-tagged-chikungunya-virus-replicons-improve-visualisation-of-non-structural-protein-3-by-fluorescence-microscopy
#16
Roland Remenyi, Grace C Roberts, Carsten Zothner, Andres Merits, Mark Harris
Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes febrile disease, muscle and joint pain, which can become chronic in some individuals. The non-structural protein 3 (nsP3) plays essential roles during infection, but a complete understanding of its function is lacking. Here we used a microscopy-based approach to image CHIKV nsP3 inside human cells. The SNAP system consists of a self-labelling enzyme tag, which catalyses the covalent linking of exogenously supplemented synthetic ligands. Genetic insertion of this tag resulted in viable replicons and specific labelling while preserving the effect of nsP3 on stress granule responses and co-localisation with GTPase Activating Protein (SH3 domain) Binding Proteins (G3BPs)...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28713953/microrna-326-inhibits-cell-proliferation-and-invasion-activating-apoptosis-in-hepatocellular-carcinoma-by-directly-targeting-lim-and-sh3-protein-1
#17
Shiping Hu, Yun Ran, Wenlin Chen, Yuncheng Zhang, Yongjian Xu
Hepatocellular carcinoma (HCC) is the fifth-most common cancer and third leading cause of cancer-related deaths worldwide. Increasing evidence indicates that dysregulation of microRNAs is often observed in HCC, and has been extensively investigated in terms of cancer formation, progression, diagnosis, therapy, and prognosis. Recently, microRNA-326 (miR-326) has been demonstrated to play important roles in multiple types of human cancer. However, the expression pattern, clinical significance, roles and regulatory mechanisms of miR-326 in HCC have yet to be elucidated...
July 12, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28712408/-dectection-of-g3bp-and-cd44v6-in-the-tissues-of-laryngeal-squamous-cell-carcinoma-and-their-clinical-significance
#18
Dahu Luo, Weihua Lou
Objective To study the expressions of RNA-binding Ras-GAP SH3 binding protein (G3BP) and tumor stem cell marker CD44v6 in laryngeal squamous cell carcinoma and their correlations with angiogenesis. Methods We collected the cancer tissues and corresponding paracancerous tissues from 56 patients with laryngeal squamous cell carcinoma. The expressions of G3BP and CD44v6 proteins were detected by Western blotting in cancer tissues and corresponding paracancerous tissues; the expressions of G3BP, CD44v6 and vascular endothelial growth factor A (VEGF-A) were tested by immunohistochemistry...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28706108/novel-function-of-a-dynein-light-chain-in-actin-assembly-during-clathrin-mediated-endocytosis
#19
Kristen B Farrell, Seth McDonald, Andrew K Lamb, Colette Worcester, Olve B Peersen, Santiago M Di Pietro
Clathrin- and actin-mediated endocytosis is essential in eukaryotic cells. In this study, we demonstrate that Tda2 is a novel protein of the endocytic machinery necessary for normal internalization of native cargo in yeast. Tda2 has not been classified in any protein family. Unexpectedly, solving the crystal structure of Tda2 revealed it belongs to the dynein light chain family. However, Tda2 works independently of the dynein motor complex and microtubules. Tda2 forms a tight complex with the polyproline motif-rich protein Aim21, which interacts physically with the SH3 domain of the Arp2/3 complex regulator Bbc1...
August 7, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28704903/enchancement-of-gamma-aminobutyric-acid-production-by-co-localization-of-neurospora-crassa-or74a-glutamate-decarboxylase-with-escherichia-coli-gaba-transporter-via-synthetic-scaffold-complex
#20
Sivachandiran Somasundaram, Murali Kannan Maruthamuthu, Irisappan Ganesh, Gyeong Tae Eom, Soon Ho Hong
Gamma-aminobutyric acid is a precusor of nylon-4, which is a promising heat-resistant biopolymer. GABA can be produced from the decarboxylation of glutamate by glutamate decarboxylase. In this study, a synthetic scaffold complex strategy was employed involving Neurospora crassa glutamate decarboxylase (GadB) and Escherichia coli GABA antiporter (GadC) to improve GABA production. To construct the complex, the SH3 domain was attached to the N. crassa GadB, and SH3 ligand was attached to the N-terminus, middle and C-terminus of E...
July 14, 2017: Journal of Microbiology and Biotechnology
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