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https://www.readbyqxmd.com/read/28333212/structural-history-of-human-srgap2-proteins
#1
Michael Sporny, Julia Guez-Haddad, Annett Kreusch, Sivan Shakartzi, Avi Neznansky, Alice Cross, Michail N Isupov, Britta Qualmann, Michael M Kessels, Yarden Opatowsky
In the development of the human brain, human-specific genes are considered to play key roles, conferring its unique advantages and vulnerabilities. At the time of Homo lineage divergence from Australopithecus, SRGAP2C gradually emerged through a process of serial duplications and mutagenesis from ancestral SRGAP2A (3.4-2.4 Ma). Remarkably, ectopic expression of SRGAP2C endows cultured mouse brain cells, with human-like characteristics, specifically, increased dendritic spine length and density. To understand the molecular mechanisms underlying this change in neuronal morphology, we determined the structure of SRGAP2A and studied the interplay between SRGAP2A and SRGAP2C...
February 21, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28319009/the-unique-domain-forms-a-fuzzy-intramolecular-complex-in-src-family-kinases
#2
Miguel Arbesú, Mariano Maffei, Tiago N Cordeiro, João M C Teixeira, Yolanda Pérez, Pau Bernadó, Serge Roche, Miquel Pons
The N-terminal regulatory region of c-Src including the SH4, Unique, and SH3 domains adopts a compact, yet highly dynamic, structure that can be described as an intramolecular fuzzy complex. Most of the long-range interactions within the Unique domain are also observed in constructs lacking the structured SH3, indicating a considerable degree of preorganization of the disordered Unique domain. Here we report that members of the Src family of kinases (SFK) share well-conserved sequence features involving aromatic residues in their Unique domains...
March 16, 2017: Structure
https://www.readbyqxmd.com/read/28316213/-expression-of-lim-and-sh3-protein-1-in-renal-clear-cell-carcinoma-and-its-effects-on-invasion-and-migration-of-renal-clear-cell-carcinoma-786-o-cells
#3
B Jin, L Gao, W Li, J C Chen, R M Wen, J Q Wang
Objective: To investigate the expression of LIM and SH3 protein 1 (LASP1) in renal cell carcinoma and its significance in the invasion and migration of renal clear cell carcinoma 786-O cell line. Methods: The expression level of LASP1 in 41 cases of renal cell carcinoma tissues and normal renal tissues was analyzed by immunohistochemistry. The relationship between the expression level of LASP1 and clinical characteristics was further analyzed. Expression of LASP1 in 10 cases of tumor tissues with or without lymph node metastasis was analyzed by Western blot...
March 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28306246/the-self-assembled-hierarchical-interfaces-of-zno-nanotubes-graphene-heterostructures-for-efficient-room-temperature-hydrogen-sensors
#4
Deepa Kathiravan, Bohr-Ran Huang, Adhimoorthy Saravanan
Herein, we report the novel nanostructural interfaces of self-assembled hierarchical ZnO nanotubes/graphene (ZNTs/G) with three different growing times of ZNTs on graphene substrates (namely, SH1, SH2 and SH3). Each sample was fabricated with interdigitated electrodes to fabricate hydrogen sensors and their hydrogen sensing properties were comprehensively studied. The systematical investigation reveals that SH1 sensor exhibits an ultra-high sensor response even at low detection level of 10 ppm (14.3%) to 100 ppm (28...
March 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28266596/bioinformatics-analysis-of-the-proteins-interacting-with-lasp-1-and-their-association-with-hbv-related-hepatocellular-carcinoma
#5
Fan-Yun Kong, Ting Zhu, Nan Li, Yun-Fei Cai, Kai Zhou, Xiao Wei, Yan-Bo Kou, Hong-Juan You, Kui-Yang Zheng, Ren-Xian Tang
LIM and SH3 domain protein (LASP-1) is responsible for the development of several types of human cancers via the interaction with other proteins; however, the precise biological functions of proteins interacting with LASP-1 are not fully clarified. Although the role of LASP-1 in hepatocarcinogenesis has been reported, the implication of LASP-1 interactors in HBV-related hepatocellular carcinoma (HCC) is not clearly evaluated. We obtained information regarding LASP-1 interactors from public databases and published studies...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28263768/osmotic-shock-induced-protein-destabilization-in-living-cells-and-its-reversal-by-glycine-betaine
#6
Samantha S Stadmiller, Annelise H Gorensek-Benitez, Alex J Guseman, Gary J Pielak
Many organisms can adapt to changes in the solute content of their surroundings (i.e., the osmolarity). Hyperosmotic shock causes water efflux and a concomitant reduction in cell volume, which is countered by the accumulation of osmolytes. This volume reduction increases the crowded nature of the cytoplasm, which is expected to affect protein stability. In contrast to traditional theory, which predicts that more crowded conditions can only increase protein stability, recent work shows that crowding can destabilize proteins through transient attractive interactions...
March 2, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28250339/the-evolutionary-appearance-of-signaling-motifs-in-pgrmc1
#7
Michael A Cahill
A complex PGRMC1-centred regulatory system controls multiple cell functions. Although PGRMC1 is phosphorylated at several positions, we do not understand the mechanisms regulating its function. PGRMC1 is the archetypal member of the membrane associated progesterone receptor (MAPR) family. Phylogentic comparison of MAPR proteins suggests that the ancestral metazoan "PGRMC-like" MAPR gene resembled PGRMC1/PGRMC2, containing the equivalents of PGRMC1 Y139 and Y180 SH2 target motifs. It later acquired a CK2 site with phosphoacceptor at S181...
February 28, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28235806/molecular-basis-of-interactions-between-sh3-domain-containing-proteins-and-the-proline-rich-region-of-the-ubiquitin-ligase-itch
#8
Guillaume Desrochers, Laurent Cappadocia, Mathieu Lussier-Price, Anh-Tien Ton, Riham Ayoubi, Adrian Serohijos, James G Omichinski, Annie Angers
The ligase Itch plays major roles in signalling pathways by inducing ubiquitylation-dependent degradation of several substrates. Substrate recognition and binding is critical for the regulation of this reaction. Like closely related ligases, Itch can interact with proteins containing a PPxY motif via its WW domains. In addition to these WW domains, Itch possesses a proline-rich region (PRR) that has been shown to interact with several Src Homology 3 (SH3) domain-containing proteins. We have previously established that despite the apparent surface uniformity and conserved fold of SH3 domains, they display different binding mechanisms and affinities for their interaction with the PRR of Itch...
February 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28235804/nitric-oxide-synthase-trafficking-inducer-is-a-pleiotropic-regulator-of-endothelial-cell-function-and-signaling
#9
Shreeta Chakraborty, Rupasri Ain
Endothelial nitric oxide synthase (eNOS) and its bioactive product nitric oxide (NO) mediate many endothelial cell functions, including angiogenesis and vascular permeability. For example, vascular endothelial growth factor (VEGF)-mediated angiogenesis is inhibited upon reduction of NO bioactivity both in vitro and in vivo. Moreover, genetic disruption or pharmacological inhibition of eNOS attenuates angiogenesis during tissue repair, resulting in delayed wound closure. These observations emphasize that eNOS-derived NO can promote angiogenesis...
February 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28235780/inhibitory-cortactin-nanobodies-delineate-the-role-of-nta-and-sh3-domain-specific-functions-during-invadopodium-formation-and-cancer-cell-invasion
#10
Laurence Bertier, Ciska Boucherie, Olivier Zwaenepoel, Berlinda Vanloo, Marleen Van Troys, Isabel Van Audenhove, Jan Gettemans
Cancer cells exploit different strategies to escape from the primary tumor, gain access to the circulation, disseminate throughout the body, and form metastases, the leading cause of death by cancer. Invadopodia, proteolytically active plasma membrane extensions, are essential in this escape mechanism. Cortactin is involved in every phase of invadopodia formation, and its overexpression is associated with increased invadopodia formation, extracellular matrix degradation, and cancer cell invasion. To analyze endogenous cortactin domain function in these processes, we characterized the effects of nanobodies that are specific for the N-terminal acidic domain of cortactin and expected to target small epitopes within this domain...
February 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28228554/association-of-lyn-kinase-with-membrane-rafts-determines-its-negative-influence-on-lps-induced-signaling
#11
Kinga Borzęcka-Solarz, Justyna Dembińska, Aneta Hromada-Judycka, Gabriela Traczyk, Anna Ciesielska, Ewelina Ziemlińska, Anna Świątkowska, Katarzyna Kwiatkowska
Lipopolysaccharide (LPS) is the component of Gram-negative bacteria which activates Toll-like receptor 4 (TLR4) to trigger pro-inflammatory responses. We examined the involvement of Lyn tyrosine kinase in TLR4 signaling of macrophages, distinguishing its catalytic activity and intermolecular interactions. For this, a series of Lyn-GFP constructs bearing point mutations in particular domains of Lyn were overexpressed in RAW264 macrophage-like cells or murine peritoneal macrophages, and their influence on LPS-induced responses was analyzed...
February 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28220894/inhibition-of-n1-src-kinase-by-a-specific-sh3-peptide-ligand-reveals-a-role-for-n1-src-in-neurite-elongation-by-l1-cam
#12
Sarah Keenan, Sarah J Wetherill, Christopher I Ugbode, Sangeeta Chawla, William J Brackenbury, Gareth J O Evans
In the mammalian brain the ubiquitous tyrosine kinase, C-Src, undergoes splicing to insert short sequences in the SH3 domain to yield N1- and N2-Src. We and others have previously shown that the N-Srcs have altered substrate specificity and kinase activity compared to C-Src. However, the exact functions of the N-Srcs are unknown and it is likely that N-Src signalling events have been misattributed to C-Src because they cannot be distinguished by conventional Src inhibitors that target the kinase domain. By screening a peptide phage display library, we discovered a novel ligand (PDN1) that targets the unique SH3 domain of N1-Src and inhibits N1-Src in cells...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28219718/a-novel-regulatory-role-of-rgs4-in-stat5b-activation-neurite-outgrowth-and-neuronal-differentiation
#13
Paschalina Pallaki, Eirini-Maria Georganta, Ioannis Serafimidis, Maria-Pagona Papakonstantinou, Vassilis Papanikolaou, Sofia Koutloglou, Elsa Papadimitriou, Adamantia Agalou, Aggeliki Tserga, Alexandra Simeonof, Dimitra Thomaidou, Maria Gaitanou, Zafiroula Georgoussi
The Regulator of G protein Signalling 4 (RGS4) is a multitask protein that interacts with and negatively modulates opioid receptor signalling. Previously, we showed that the δ-opioid receptor (δ-OR) forms a multiprotein signalling complex consisting of Gi/Go proteins and the Signal Transducer and Activator of Transcription 5B (STAT5B) that leads to neuronal differentiation and neurite outgrowth upon δ-ΟR activation. Here, we investigated whether RGS4 could participate in signalling pathways to regulate neurotropic events...
February 17, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28183734/skap2-is-required-for-%C3%AE-2-integrin-mediated-neutrophil-recruitment-and-functions
#14
Mark Boras, Stephanie Volmering, Arne Bokemeyer, Jan Rossaint, Helena Block, Bernadette Bardel, Veerle Van Marck, Barbara Heitplatz, Stefanie Kliche, Annegret Reinhold, Clifford Lowell, Alexander Zarbock
Integrin activation is required for neutrophil functions. Impaired integrin activation on neutrophils is the hallmark of leukocyte adhesion deficiency (LAD) syndrome in humans, characterized by impaired leukocyte recruitment and recurrent infections. The Src kinase-associated phosphoprotein 2 (Skap2) is involved in integrin functions in different leukocyte subtypes. However, the role of Skap2 in β2 integrin activation and neutrophil recruitment is unknown. In this study, we demonstrate the crucial role of Skap2 in regulating actin polymerization and binding of talin-1 and kindlin-3 to the β2 integrin cytoplasmic domain, thereby being indispensable for β2 integrin activation and neutrophil recruitment...
March 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28179641/shank-proteins-roles-at-the-synapse-and-in-autism-spectrum-disorder
#15
REVIEW
Patricia Monteiro, Guoping Feng
Several large-scale genomic studies have supported an association between cases of autism spectrum disorder and mutations in the genes SH3 and multiple ankyrin repeat domains protein 1 (SHANK1), SHANK2 and SHANK3, which encode a family of postsynaptic scaffolding proteins that are present at glutamatergic synapses in the CNS. An evaluation of human genetic data, as well as of in vitro and in vivo animal model data, may allow us to understand how disruption of SHANK scaffolding proteins affects the structure and function of neural circuits and alters behaviour...
March 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/28156097/confinement-and-stabilization-of-fyn-sh3-folding-intermediate-mimetics-within-the-cavity-of-the-chaperonin-groel-demonstrated-by-relaxation-based-nmr
#16
David S Libich, Vitali Tugarinov, Rodolfo Ghirlando, G Marius Clore
The interaction of two folding intermediate mimetics of the model protein substrate Fyn SH3 with the chaperonin GroEL, a supramolecular foldase/unfoldase machine, has been investigated by (15)N relaxation-based nuclear magnetic resonance spectroscopy (lifetime line broadening, dark state exchange saturation transfer, and relaxation dispersion). The two mimetics comprise C-terminal truncations of wild-type and triple-mutant (A39V/N53P/V55L) Fyn SH3 in which the C-terminal strand of the SH3 domain is unfolded, while preserving the remaining domain structure...
February 8, 2017: Biochemistry
https://www.readbyqxmd.com/read/28138250/correlation-of-sash1-expression-and-ultrasonographic-features-in-breast-cancer
#17
Xuchu Gong, Jinna Wu, Jian Wu, Jun Liu, Hailin Gu, Hao Shen
OBJECTIVE: SASH1 is a member of the SH3/SAM adapter molecules family and has been identified as a new tumor suppressor and critical protein in signal transduction. An ectopic expression of SASH1 is associated with decreased cell viability of breast cancer. The aim of this study was to explore the association between SASH1 expression and the ultrasonographic features in breast cancer. PATIENTS AND METHODS: A total of 186 patients diagnosed with breast cancer were included in this study...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28127816/the-idl-of-e-coli-ssb-links-ssdna-and-protein-binding-by-mediating-protein-protein-interactions
#18
Piero R Bianco, Sasheen Pottinger, Hui Yin Tan, Trong Nguyenduc, Kervin Rex, Umesh Varshney
The E. coli single strand DNA binding protein (SSB) is essential to viability where it functions in two seemingly disparate roles: it binds to single stranded DNA (ssDNA) and to target proteins that comprise the SSB interactome. The link between these roles resides in a previously under-appreciated region of the protein known as the intrinsically disordered linker (IDL). We present a model wherein the IDL is responsible for mediating protein-protein interactions critical to each role. When interactions occur between SSB tetramers, cooperative binding to ssDNA results...
February 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28118077/midbody-localization-of-vinexin-recruits-rhotekin-to-facilitate-cytokinetic-abscission
#19
Yu-Wei Chang, Yi-Shuian Huang
Vinexin is a SH3 domain-containing adaptor protein that has diverse roles in cell adhesion, signal transduction, gene regulation and stress granule assembly. In this study, we found that vinexin localizes at the midbody during cell division and facilitates cytokinesis. Knockdown of vinexin in HeLa cells delayed the mitotic cell cycle progression and increased the time of cell abscission and the failure to resolve the cytoplasmic bridge. Midbody-localized vinexin is essential for recruiting rhotekin to this structure for cytokinesis because overexpression of a vinexin mutant without a rhotekin-binding motif or knockdown of rhotekin also impaired cytokinetic abscission and increased the number of cells arrested at the midbody stage...
January 24, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28112192/stac3-stably-interacts-through-its-c1-domain-with-cav1-1-in-skeletal-muscle-triads
#20
Marta Campiglio, Bernhard E Flucher
The adaptor protein STAC3 is essential for skeletal muscle excitation-contraction (EC) coupling and a mutation in the STAC3 gene has been linked to a severe muscle disease, Native American myopathy (NAM). However the function of STAC3, its interaction partner, and the mode of interaction within the EC-coupling complex remained elusive. Here we demonstrate that STAC3 forms a stable interaction with the voltage-sensor of EC-coupling, CaV1.1, and that this interaction depends on a hitherto unidentified protein-protein binding pocket in the C1 domain of STAC3...
January 23, 2017: Scientific Reports
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