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https://www.readbyqxmd.com/read/28730474/allosteric-modulation-of-src-family-kinases-with-atp-competitive-inhibitors
#1
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
#2
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
#3
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
#4
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
#5
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...
July 13, 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
#6
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
https://www.readbyqxmd.com/read/28701918/striatal-transcriptome-and-interactome-analysis-of-shank3-overexpressing-mice-reveals-the-connectivity-between-shank3-and-mtorc1-signaling
#7
Yeunkum Lee, Sun Gyun Kim, Bokyoung Lee, Yinhua Zhang, Yoonhee Kim, Shinhyun Kim, Eunjoon Kim, Hyojin Kang, Kihoon Han
Mania causes symptoms of hyperactivity, impulsivity, elevated mood, reduced anxiety and decreased need for sleep, which suggests that the dysfunction of the striatum, a critical component of the brain motor and reward system, can be causally associated with mania. However, detailed molecular pathophysiology underlying the striatal dysfunction in mania remains largely unknown. In this study, we aimed to identify the molecular pathways showing alterations in the striatum of SH3 and multiple ankyrin repeat domains 3 (Shank3)-overexpressing transgenic (TG) mice that display manic-like behaviors...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28682056/a-dry-transition-state-more-compact-than-the-native-state-is-stabilized-by-non-native-interactions-during-the-unfolding-of-a-small-protein
#8
Sreemantee Sen, Rama Reddy Goluguri, Jayant B Udgaonkar
To define the role of non-native interactions in directing the course of protein folding or unfolding reactions, has been a difficult challenge. In particular, it is not known to what extent such interactions play a productive role by stabilizing the structures of transition states (TSs) found on the folding and unfolding pathways of proteins. On the contrary, it is thought that the TSs are expanded forms of the native (N) state stabilized by native interactions, and it is not known whether non-native interactions can modulate TS structure...
July 6, 2017: Biochemistry
https://www.readbyqxmd.com/read/28679293/sh3bgrl-as-a-novel-prognostic-biomarker-is-down-regulated-in-acute-myeloid-leukemia
#9
Limei Xu, Mingming Zhang, Hui Li, Wen Guan, Bin Liu, Fengqi Liu, Hehua Wang, Juan Li, Shulan Yang, Xiuzhen Tong, Haihe Wang
Phosphatase PRL-3 expression is positively associated to acute myeloid leukemia (AML) progression and drug resistance. SH3-domain-binding glutamic acid-rich protein-like protein (SH3BGRL), a downstream effector of PRL-3, plays a tumor suppressive role in solid tumors, but it remains elusive in AML. Here, we followed up and validated the relevance of SH3BGRL expression to AML progression in 116 cases. Results showed that SH3BGRL is down-regulated in 62.37% AML cases with poor prognosis. Cases with positive response to therapy accompanies with SH3GRL expression restoration...
July 6, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28667917/identification-of-peptide-mediated-interactions-between-human-pttg-and-sh3-domains-in-pall-gene-expression-profile
#10
Tingting Yan, Xiangxiang Shi, Jing Fu
Human pituitary tumor-transforming gene (PTTG) plays an essential role in the development and progression of pediatric acute lymphoblastic leukemia (pALL). PTTG has two SH3-binding peptide motifs that can be recognized by a variety of SH3-containing proteins in the pALL through peptide-mediated interactions. In this study, the gene expression profile of pALL was examined in detail by integrating computational modeling and experimental assay, aiming to identify those potential partner proteins of human PTTG...
June 26, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28667800/lasp2-enhances-tumor-invasion-via-facilitating-phosphorylation-of-fak-and-predicts-poor-overall-survival-of-non-small-cell-lung-cancer-patients
#11
Xiupeng Zhang, Lin Cai, Haijing Zhou, Yang Liu, Chuifeng Fan, Liang Wang, Ailin Li, Yuan Miao, Qingchang Li, Xueshan Qiu, Enhua Wang
Lasp2, as well as Lasp1, is a member of the LIM-protein subfamily of the nebulin group characterized by the combined presence of LIM and SH3 domains. Lasp1 and Lasp2 are highly conserved in their LIM, nebulin-like and SH3 domains but differ significantly at their linker regions. Lasp1 had been described as an oncogenic protein that was highly expressed in diverse cancer types and facilitated tumor proliferation, invasion and metastasis process. However, unlike Lasp1, little is known about the functions of Lasp2...
July 1, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28667327/intermolecular-steric-inhibition-of-ephexin4-is-relieved-by-elmo1
#12
Kwanhyeong Kim, Juyeon Lee, Sang-Ah Lee, Hyunji Moon, Boyeon Park, Deokhwan Kim, Young-Eun Joo, Daeho Park
Ephexin4, a guanine nucleotide-exchange factor for RhoG, promotes engulfment of apoptotic cells and cancer cell migration in a RhoG-dependent manner, which is synergistically augmented by Elmo1, an Ephexin4-interacting protein. However, the underlying molecular mechanism remains elusive. Here, we report a mechanism by which Elmo1 cooperates with Ephexin4 to activate RhoG. We found that Ephexin4 activity was increased by elimination of its SH3 domain which intermolecularly interacts with the N20 region of Ephexin4...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28665107/stepwise-assembly-of-%C3%AE-sheet-structure-during-the-folding-of-an-sh3-domain-revealed-by-a-pulsed-hydrogen-exchange-mass-spectrometry-study
#13
Nilesh Aghera, Jayant B Udgaonkar
Dissecting temporally the sequence of secondary structural changes, and determining how these specific changes modulate conformational heterogeneity, remain major goals of protein folding studies. In this study, the folding of the SH3 domain of PI3 kinase has been characterized using pulsed hydrogen exchange mass spectrometry (HX-MS). The folding could be described as a four-state process, U ↔ IVE ↔ IE ↔ N, where IVE and IE are structurally heterogeneous intermediate ensembles. Compared to U, early intermediate IVE has a marginally increased level of protection against HX of amides along the entire length of the polypeptide...
July 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28664153/sopb-mediated-recruitment-of-snx18-facilitates-salmonella-typhimurium-internalization-by-the-host-cell
#14
David Liebl, Xiaying Qi, Yang Zhe, Timothy C Barnett, Rohan D Teasdale
To invade epithelial cells, Salmonella enterica serovar Typhimurium (S. Typhimurium) induces macropinocytosis through the action of virulence proteins delivered across the host cell membrane via a type III secretion system. We show that after docking at the plasma membrane S. Typhimurium triggers rapid recruitment of cytosolic SNX18, a SH3-PX-BAR domain sorting nexin protein, to the bacteria-induced membrane ruffles and to the nascent Salmonella-containing vacuole. SNX18 recruitment required the inositol-phosphatase activity of the Salmonella effector SopB and an intact phosphoinositide-binding site within the PX domain of SNX18, but occurred independently of Rho-GTPases Rac1 and Cdc42 activation...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28663287/carmil-family-proteins-as-multidomain-regulators-of-actin-based-motility
#15
Benjamin C Stark, M Hunter Lanier, John A Cooper
CARMILs are large multidomain proteins that regulate the actin-binding activity of capping protein (CP), a major capper of actin filament barbed ends in cells. CARMILs bind directly to CP and induce a conformational change that allosterically decreases but does not abolish its actin-capping activity. The CP-binding domain of CARMIL consists of the CP-interaction (CPI) and CARMIL-specific interaction (CSI) motifs, which are arranged in tandem. Many cellular functions of CARMILs require the interaction with CP; however, a more surprising result is that the cellular function of CP in cells appears to require binding to a CARMIL or another protein with a CPI motif, suggesting that CPI-motif proteins target CP and modulate its actin-capping activity...
July 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28655565/environmental-enrichment-attenuates-behavioral-abnormalities-in-valproic-acid-exposed-autism-model-mice
#16
Hiroshi Yamaguchi, Yuta Hara, Yukio Ago, Erika Takano, Shigeru Hasebe, Takanobu Nakazawa, Hitoshi Hashimoto, Toshio Matsuda, Kazuhiro Takuma
We recently demonstrated that prenatal exposure to valproic acid (VPA) at embryonic day 12.5 causes autism spectrum disorder (ASD)-like phenotypes such as hypolocomotion, anxiety-like behavior, social deficits and cognitive impairment in mice and that it decreases dendritic spine density in the hippocampal CA1 region. Previous studies show that some abnormal behaviors are improved by environmental enrichment in ASD rodent models, but it is not known whether environmental enrichment improves cognitive impairment...
June 24, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28650961/mfpred-rapid-and-accurate-prediction-of-protein-peptide-recognition-multispecificity-using-self-consistent-mean-field-theory
#17
Aliza B Rubenstein, Manasi A Pethe, Sagar D Khare
Multispecificity-the ability of a single receptor protein molecule to interact with multiple substrates-is a hallmark of molecular recognition at protein-protein and protein-peptide interfaces, including enzyme-substrate complexes. The ability to perform structure-based prediction of multispecificity would aid in the identification of novel enzyme substrates, protein interaction partners, and enable design of novel enzymes targeted towards alternative substrates. The relatively slow speed of current biophysical, structure-based methods limits their use for prediction and, especially, design of multispecificity...
June 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28647360/structure-of-an-unconventional-sh3-domain-from-the-postsynaptic-density-protein-shank3-at-ultrahigh-resolution
#18
Srinivas Kumar Ponna, Matti Myllykoski, Tobias M Boeckers, Petri Kursula
The Shank family comprises three large multi-domain proteins playing central roles as protein scaffolds in the neuronal postsynaptic density. The Shank proteins are closely linked to neuropsychiatric diseases, such as autism spectrum disorders. One characteristic domain in the Shank family is the SH3 domain, assumed to play a role in protein-protein interactions; however, no specific ligand binding to any Shank SH3 domain has been described. We solved the crystal structure of the SH3 domain from Shank3 at sub-atomic resolution...
June 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28646413/integrated-in-silico-in-vitro-identification-and-characterization-of-the-sh3-mediated-interaction-between-human-pttg-and-its-cognate-partners-in-medulloblastoma
#19
Jiangang Liu, Dapeng Wang, Yanyan Li, Hui Yao, Nan Zhang, Xuewen Zhang, Fangping Zhong, Yulun Huang
The human pituitary tumor-transforming gene is an oncogenic protein which serves as a central hub in the cellular signaling network of medulloblastoma. The protein contains two vicinal PxxP motifs at its C terminus that are potential binding sites of peptide-recognition SH3 domains. Here, a synthetic protocol that integrated in silico analysis and in vitro assay was described to identify the SH3-binding partners of pituitary tumor-transforming gene in the gene expression profile of medulloblastoma. In the procedure, a variety of structurally diverse, non-redundant SH3 domains with high gene expression in medulloblastoma were compiled, and their three-dimensional structures were either manually retrieved from the protein data bank database or computationally modeled through bioinformatics technique...
June 24, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28625920/c-terminal-tail-of-nadph-oxidase-organizer-1-noxo1-mediates-interaction-with-nadph-oxidase-activator-noxa1-in-the-nox1-complex
#20
Pravesh Shrestha, Ji-Hye Yun, Yoon-Joo Ko, Myeongkyu Kim, Yun Soo Bae, Weontae Lee
NOX1 (NADPH oxidase) similar to phagocyte NADPH oxidase, is expressed mainly in the colon epithelium and it is responsible for host defense against microbial infections by generating ROS (reactive oxygen species). NOX1 is activated by two regulatory cytosolic proteins that form a hetero-dimer, Noxo1 (NOX organizer 1) and Noxa1 (NOX activator 1). The interaction between Noxa1 and Noxo1 is critical for activating NOX1. However no structural studies for interaction between Noxa1 and Noxo1 has not been reported till date...
June 16, 2017: Biochemical and Biophysical Research Communications
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