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https://www.readbyqxmd.com/read/29146598/structural-analyses-unravel-the-molecular-mechanism-of-cyclic-di-gmp-regulation-of-bacterial-chemotaxis-via-a-pilz-adaptor-protein
#1
Xin-Fu Yan, Lingyi Xin, Jackie Tan Yen, Yukai Zeng, Shengyang Jin, Qing Wei Cheang, Rachel Andrea Chea Yuen Fong, Keng-Hwee Chiam, Zhao-Xun Liang, Yong-Gui Gao
The bacterial second messenger cyclic di-GMP (c-di-GMP) has emerged as a prominent mediator of bacterial physiology, motility and pathogenicity. Cdi-GMP often regulates the function of its protein targets through a unique mechanism that involves a discrete PilZ adaptor protein. However, the molecular mechanism in c-di-GMP-mediated protein regulation is unclear. Here, we present the structure of the PilZ adaptor protein MapZ co-crystallized in complex with c-di-GMP and its protein target CheR1, a chemotaxis-regulating methyltransferase in Pseudomonas aeruginosa This co-crystal structure, together with the structure of free CheR1, revealed that the binding of c-di-GMP induces dramatic structural changes in MapZ that are crucial for CheR1 binding...
November 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29144391/antimicrobial-peptide-epinecidin-1-modulates-myd88-protein-levels-via-the-proteasome-degradation-pathway
#2
Bor-Chyuan Su, Jyh-Yih Chen
The cationic antimicrobial peptide epinecidin-1 was identified from Epinephelus coioides and possesses multiple biological functions, including antibacterial, antifungal, anti-tumor, and immunomodulatory effects. In addition, epinecidin-1 suppresses lipopolysaccharide (LPS)-induced inflammation by neutralizing LPS and ameliorating LPS/Toll-like receptor (TLR)-4 internalization. However, it is unclear whether the actions of epinecidin-1 depend on the regulation of TLR adaptor protein MyD88 or endogenous TLR signaling antagonists, which include A20, interleukin-1 receptor associated kinase (IRAK)-M, and suppressor of cytokine signaling (SOCS)-1...
November 16, 2017: Marine Drugs
https://www.readbyqxmd.com/read/29142073/gga1-regulates-signal-dependent-sorting-of-bace1-to-recycling-endosomes-which-moderates-a%C3%AE-production
#3
Wei Hong Toh, Pei Zhi Cheryl Chia, Mohammed Iqbal Hossain, Paul A Gleeson
The diversion of the membrane-bound β-secretase BACE1 from the endo-lysosomal pathway to recycling endosomes represents an important transport step in the regulation of amyloid beta (Aβ) production. However, the mechanisms that regulate endosome sorting of BACE1 are poorly understood. Here we assessed the transport of BACE1 from early to recycling endosomes and have identified essential roles for the SNX4-mediated, signal independent pathway and for a novel signal-mediated pathway. The signal-mediated pathway is regulated by the phosphorylation of the acidic cluster-dileucine DISLL cytoplasmic tail motif of BACE1...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29138488/structural-basis-of-adaptor-mediated-protein-degradation-by-the-tail-specific-pdz-protease-prc
#4
Ming-Yuan Su, Nilanjan Som, Chia-Yun Wu, Shih-Chieh Su, Yi-Ting Kuo, Lu-Chu Ke, Meng-Ru Ho, Shiou-Ru Tzeng, Ching-Hao Teng, Dominique Mengin-Lecreulx, Manjula Reddy, Chung-I Chang
Peptidoglycan (PG) is a highly cross-linked, protective mesh-like sacculus that surrounds the bacterial cytoplasmic membrane. Expansion of PG is tightly coupled to growth of a bacterial cell and requires hydrolases to cleave the cross-links for insertion of nascent PG material. In Escherichia coli, a proteolytic system comprising the periplasmic PDZ-protease Prc and the lipoprotein adaptor NlpI contributes to PG enlargement by regulating cellular levels of MepS, a cross-link-specific hydrolase. Here, we demonstrate how NlpI binds Prc to facilitate the degradation of its substrate MepS by structural and mutational analyses...
November 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/29138318/snare-priming-is-essential-for-maturation-of-autophagosomes-but-not-for-their-formation
#5
Adi Abada, Smadar Levin-Zaidman, Ziv Porat, Tali Dadosh, Zvulun Elazar
Autophagy, a unique intracellular membrane-trafficking pathway, is initiated by the formation of an isolation membrane (phagophore) that engulfs cytoplasmic constituents, leading to generation of the autophagosome, a double-membrane vesicle, which is targeted to the lysosome. The outer autophagosomal membrane consequently fuses with the lysosomal membrane. Multiple membrane-fusion events mediated by SNARE molecules have been postulated to promote autophagy. αSNAP, the adaptor molecule for the SNARE-priming enzyme N-ethylmaleimide-sensitive factor (NSF) is known to be crucial for intracellular membrane fusion processes, but its role in autophagy remains unclear...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29137271/environmental-conditions-differentially-affect-neurobehavioral-outcomes-in-a-mouse-model-of-sepsis-associated-encephalopathy
#6
Mu-Huo Ji, Hui Tang, Dan Luo, Li-Li Qiu, Min Jia, Hong-Mei Yuan, Shan-Wu Feng, Jian-Jun Yang
Brain dysfunction remains a common complication after sepsis development and is an independent risk factor for a poorer prognosis and an increased mortality. Here we tested the hypothesis that the behavioral outcomes after lipopolysaccharides (LPS) administration are exacerbated by an impoverished environment (IE) and alleviated by an enriched environment (EE), respectively. Mice were randomly allocated in a standard environment (SE), an EE, or an IE for 4 weeks after LPS or normal saline (NS) administration...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135573/evidence-of-inflammasome-activation-and-formation-of-monocyte-derived-apoptosis-associated-speck-like-protein-containing-a-caspase-recruitment-domain-specks-in-hiv-1-positive-patients
#7
Fareed Ahmad, Neha Mishra, Gerrit Ahrenstorf, Bernardo S Franklin, Eicke Latz, Reinhold E Schmidt, Lukas Bossaller
OBJECTIVE: The formation of large intracellular protein aggregates of the inflammasome adaptor apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) (PYCARD) is a hallmark of inflammasome activation. ASC speck-forming cells release the highly proinflammatory cytokine IL-1β in addition to ASC specks into the extracellular space during pyroptotic cell death. There ASC specks can propagate inflammation to other nonactivated cells or tissues. HIV-1 retroviral infection triggers inflammasome activation of abortively infected CD4 T cells in secondary lymphatic tissues...
November 10, 2017: AIDS
https://www.readbyqxmd.com/read/29133402/assigning-chemoreceptors-to-chemosensory-pathways-in-pseudomonas-aeruginosa
#8
Davi R Ortega, Aaron D Fleetwood, Tino Krell, Caroline S Harwood, Grant J Jensen, Igor B Zhulin
In contrast to Escherichia coli, a model organism for chemotaxis that has 5 chemoreceptors and a single chemosensory pathway, Pseudomonas aeruginosa PAO1 has a much more complex chemosensory network, which consists of 26 chemoreceptors feeding into four chemosensory pathways. While several chemoreceptors were rigorously linked to specific pathways in a series of experimental studies, for most of them this information is not available. Thus, we addressed the problem computationally. Protein-protein interaction network prediction, coexpression data mining, and phylogenetic profiling all produced incomplete and uncertain assignments of chemoreceptors to pathways...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29133316/study-protocol-for-think-a-multinational-open-label-phase-i-study-to-assess-the-safety-and-clinical-activity-of-multiple-administrations-of-nkr-2-in-patients-with-different-metastatic-tumour-types
#9
Caroline Lonez, Bikash Verma, Alain Hendlisz, Philippe Aftimos, Ahmad Awada, Eric Van Den Neste, Gaetan Catala, Jean-Pascal H Machiels, Fanny Piette, Jason B Brayer, David A Sallman, Tessa Kerre, Kunle Odunsi, Marco L Davila, David E Gilham, Frédéric F Lehmann
INTRODUCTION: NKR-2 are autologous T cells genetically modified to express a chimeric antigen receptor (CAR) comprising a fusion of the natural killer group 2D (NKG2D) receptor with the CD3ζ signalling domain, which associates with the adaptor molecule DNAX-activating protein of 10 kDa (DAP10) to provide co-stimulatory signal upon ligand binding. NKG2D binds eight different ligands expressed on the cell surface of many tumour cells and which are normally absent on non-neoplastic cells...
November 12, 2017: BMJ Open
https://www.readbyqxmd.com/read/29132350/avian-infectious-bronchitis-virus-disrupts-the-melanoma-differentiation-associated-gene-5-mda5-signaling-pathway-by-cleavage-of-the-adaptor-protein-mavs
#10
Liping Yu, Xiaorong Zhang, Tianqi Wu, Jin Su, Yuyang Wang, Yuexin Wang, Baoyang Ruan, Xiaosai Niu, Yantao Wu
BACKGROUND: Melanoma differentiation associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I) selectively sense cytoplasmic viral RNA to induce an antiviral immune response. Infectious bronchitis virus (IBV) is one of the most important infectious agents in chickens, and in chicken cells, it can be recognized by MDA5 to activate interferon production. RIG-I is considered to be absent in chickens. However, the absence of RIG-I in chickens raises the question of whether this protein influences the antiviral immune response against IBV infection...
November 13, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29131484/the-major-cellulases-cbh-1-and-cbh-2-of-neurospora-crassa-rely-on-distinct-er-cargo-adaptors-for-efficient-er-exit
#11
Trevor Starr, A Pedro Gonçalves, Neeka Meshgin, N Louise Glass
Filamentous fungi are native secretors of lignocellulolytic enzymes and are used as protein-producing factories in the industrial biotechnology sector. Despite the importance of these organisms in industry, relatively little is known about the filamentous fungal secretory pathway or how it might be manipulated for improved protein production. Here we use Neurospora crassa as a model filamentous fungus to interrogate the requirements for trafficking of cellulase enzymes from the endoplasmic reticulum to the Golgi...
November 13, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/29128729/recent-advances-in-inflammasome-biology
#12
REVIEW
David E Place, Thirumala-Devi Kanneganti
The inflammasome is a complex of proteins that through the activity of caspase-1 and the downstream substrates gasdermin D, IL-1β, and IL-18 execute an inflammatory form of cell death termed pyroptosis. Activation of this complex often involves the adaptor protein ASC and upstream sensors including NLRP1, NLRP3, NLRC4, AIM2, and pyrin, which are activated by different stimuli including infectious agents and changes in cell homeostasis. Here we discuss new regulatory mechanisms that have been identified for the canonical inflammasomes, the most recently identified NLRP9b inflammasome, and the new gasdermin family of proteins that mediate pyroptosis and other forms of regulated cell death...
November 9, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29128526/functional-analysis-of-cullin-3-e3-ligases-in-tumorigenesis
#13
REVIEW
Ji Cheng, Jianping Guo, Zhiwei Wang, Brian J North, Kaixiong Tao, Xiangpeng Dai, Wenyi Wei
Cullin 3-RING ligases (CRL3) play pivotal roles in the regulation of various physiological and pathological processes, including neoplastic events. The substrate adaptors of CRL3 typically contain a BTB domain that mediates the interaction between Cullin 3 and target substrates to promote their ubiquitination and subsequent degradation. The biological implications of CRL3 adaptor proteins have been well described where they have been found to play a role as either an oncogene, tumor suppressor, or can mediate either of these effects in a context-dependent manner...
November 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29127708/calcimimetic-and-calcilytic-therapies-for-inherited-disorders-of-the-calcium-sensing-receptor-signalling-pathway
#14
REVIEW
Fadil M Hannan, Mie K Olesen, Rajesh V Thakker
THE CALCIUM-SENSING RECEPTOR (CAS RECEPTOR) PLAYS A PIVOTAL ROLE IN EXTRACELLULAR CALCIUM HOMEOSTASIS AND GERMLINE LOSS- AND GAIN-OF-FUNCTION MUTATIONS CAUSE FAMILIAL HYPOCALCIURIC HYPERCALCAEMIA (FHH) AND AUTOSOMAL DOMINANT HYPOCALCAEMIA (ADH), RESPECTIVELY. CAS RECEPTOR SIGNAL TRANSDUCTION IN THE PARATHYROID GLANDS IS LIKELY REGULATED BY G-PROTEIN SUBUNIT Α11 (GΑ11) AND ADAPTOR-RELATED PROTEIN COMPLEX-2 SIGMA SUBUNIT (AP2Σ), AND RECENT STUDIES HAVE IDENTIFIED GERMLINE MUTATIONS OF THESE PROTEINS AS A CAUSE OF FHH AND/OR ADH...
November 11, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29127148/ubc9-binds-to-adap-and-is-required-for-rap1-membrane-recruitment-rac1-activation-and-integrin-mediated-t-cell-adhesion
#15
Yiwei Xiong, Chengjin Ye, Naiqi Yang, Madanqi Li, Hebin Liu
Although the immune adaptor adhesion and degranulation-promoting adaptor protein (ADAP) acts as a key mediator of integrin inside-out signaling leading to T cell adhesion, the regulation of this adaptor during integrin activation and clustering remains unclear. We now identify Ubc9, the sole small ubiquitin-related modifier E2 conjugase, as an essential regulator of ADAP where it is required for TCR-induced membrane recruitment of the small GTPase Rap1 and its effector protein RapL and for activation of the small GTPase Rac1 in T cell adhesion...
November 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29126932/docosahexaenoic-acid-dha-enhances-the-therapeutic-potential-of-neonatal-neural-stem-cell-transplantation-post-traumatic-brain-injury
#16
Hussein Ghazale, Naify Ramadan, Sara Mantash, Kazem Zibara, Sally El-Sitt, Hala Darwish, Farah Chamaa, Rose Mary Boustany, Stefania Mondello, Wassim Abou-Kheir, Jihane Soueid, Firas Kobeissy
Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide with 1.5 million people inflicted yearly. Several neurotherapeutic interventions have been proposed including drug administration as well as cellular therapy involving neural stem cells (NSCs). Among the proposed drugs is docosahexaenoic acid (DHA), a polyunsaturated fatty acid, exhibiting neuroprotective properties. In this study, we utilized an innovative intervention of neonatal NSCs transplantation in combination with DHA injections in order to ameliorate brain damage and promote functional recovery in an experimental model of TBI...
November 7, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29126745/xenophagic-pathways-and-their-bacterial-subversion-in-cellular-self-defense-%C3%AF-%C3%AE-%C3%AE-%C3%AF-%C3%AE-%C3%AF-%C3%AE%C2%B5%C3%AE-everything-is-in-flux
#17
REVIEW
Nadine Radomski, Annica Rebbig, Ralf M Leonhardt, Michael R Knittler
Autophagy is an evolutionarily ancient and highly conserved eukaryotic mechanism that targets cytoplasmic material for degradation. Autophagic flux involves the formation of autophagosomes and their degradation by lysosomes. The process plays a crucial role in maintaining cellular homeostasis and responds to various environmental conditions. While autophagy had previously been thought to be a non-selective process, it is now clear that it can also selectively target cellular organelles, such as mitochondria (referred to as mitophagy) and/or invading pathogens (referred to as xenophagy)...
November 2, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/29125705/m-tuberculosis-mce3c-promotes-mycobacteria-entry-into-macrophages-through-activation-of-%C3%AE-2-integrin-mediated-signaling-pathway
#18
Yong Zhang, Jie Li, Bingxi Li, Jing Wang, Cui Hua Liu
Establishment of infection by facultative intracellular pathogen Mycobacterium tuberculosis (Mtb) requires adherence to and internalization by macrophages. However, the effector molecules exploited by Mtb for entry into macrophages remain to be fully understood. The mammalian cell entry (Mce) proteins play an essential role in facilitating the internalization of mycobacteria into mammalian cells. Here we characterized Mtb Mce3C as a new mycobacterial surface protein that could promote mycobacterial adhesion to and invasion of macrophages in an RGD motif-dependent manner...
November 10, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/29123523/identification-of-an-evolutionarily-conserved-ankyrin-domain-containing-protein-caiap-which-regulates-inflammasome-dependent-resistance-to-bacterial-infection
#19
Sylwia D Tyrkalska, Sergio Candel, Ana B Pérez-Oliva, Ana Valera, Francisca Alcaraz-Pérez, Diana García-Moreno, María L Cayuela, Victoriano Mulero
Many proteins contain tandemly repeated modules of several amino acids, which act as the building blocks that form the underlying architecture of a specific protein-binding interface. Among these motifs and one of the most frequently observed is ankyrin repeats (ANK), which consist of 33 amino acid residues that are highly conserved. ANK domains span a wide range of functions, including protein-protein interactions, such as the recruitment of substrate to the catalytic domain of an enzyme, or the assembly of stable multiprotein complexes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29123520/dexd-h-box-helicase-36-signaling-via-myeloid-differentiation-primary-response-gene-88-contributes-to-nf-%C3%AE%C2%BAb-activation-to-type-2-porcine-reproductive-and-respiratory-syndrome-virus-infection
#20
Huiyuan Jing, Yanrong Zhou, Liurong Fang, Zhen Ding, Dang Wang, Wenting Ke, Huanchun Chen, Shaobo Xiao
DExD/H-box helicase 36 (DHX36) is known to be an ATP-dependent RNA helicase that unwinds the guanine-quadruplexes DNA or RNA, but emerging data suggest that it also functions as pattern recognition receptor in innate immunity. Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has been devastating the swine industry worldwide. Interstitial pneumonia is considered to be one of the most obvious clinical signs of PRRSV infection, suggesting that the inflammatory response plays an important role in PRRSV pathogenesis...
2017: Frontiers in Immunology
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