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Complex assembly

Jeffrey D Nanson, Bostjan Kobe, Thomas Ve
The innate immune system consists of pattern recognition receptors (PRRs) that detect pathogen- and endogenous danger-associated molecular patterns (PAMPs and DAMPs), initiating signaling pathways that lead to the induction of cytokine expression, processing of pro-inflammatory cytokines, and induction of cell-death responses. An emerging concept in these pathways and associated processes is signaling by cooperative assembly formation (SCAF), which involves formation of higher order oligomeric complexes, and enables rapid and strongly amplified signaling responses to minute amounts of stimulus...
December 5, 2018: Journal of Leukocyte Biology
Srijeeb Karmakar, Laipubam Gayatri Sharma, Abhishek Roy, Anjali Patel, Lalit Mohan Pandey
SNARE (Soluble NSF(N-ethylmaleimide-sensitive factor) Attachment Receptor) complex is a trimeric supramolecular organization of SNAP25, syntaxin, and VAMP which mediates fusion of synaptic vesicles with the presynaptic plasma membrane. The functioning of this entire protein assembly is dependent on its tetrahelical coiled coil structure alongside its interaction with a large spectrum of regulatory proteins like synaptotagmin, complexin, intersectin, etc. Defects arising in SNARE complex assembly due to mutations or faulty post-translational modifications are associated to severe synaptopathies like Schizophrenia and also proteopathies like Alzheimer's disease...
December 2, 2018: Neurochemistry International
Erich Michel, Oliver Zerbe, Andreas Plückthun
Designed armadillo repeat proteins (dArmRPs) are modular peptide binders composed of N- and C-terminal capping repeats Y and A and a variable number of internal modules M that each specifically recognize two amino acids of the target peptide. Complementary fragments of dArmRPs obtained by splitting the protein between helices H1 and H2 of an internal module show conditional and specific assembly only in presence of a target peptide (Michel et al., 2018). Here, we investigate dArmRP fragments that already spontaneously assemble with high affinity, e...
December 1, 2018: Biological Chemistry
Yoko Sakata, Ryoichi Yamamoto, Daiki Saito, Yuko Tamura, Keisuke Maruyama, Tomoki Ogoshi, Shigehisa Akine
A triptycene-based shape-persistent belt-shaped macrocycle, metallonanobelt, was synthesized by the self-assembly of 2,3,6,7-tetraaminotriptycene L and square planar Pd2+ . The pentamer was selectively formed by the complexation of L with Pd2+ in the presence of the pillar[6]arene derivative P6 having triethylene glycol pendant as a template, whereas a mixture of a trimer, tetramer, and pentamer was obtained in the absence of the template. The pentamer was successfully isolated based on the solubility difference between the metallonanobelt and the template...
December 5, 2018: Inorganic Chemistry
Yang Zhang, Jingyi Zou, Xiaomin Zhao, Zhenghong Yuan, Zhigang Yi
Daclatasvir (DCV) is a highly potent direct-acting antiviral that targets the non-structural protein 5A (NS5A) of hepatitis C virus (HCV) and has been used with great clinical success. Previous studies have demonstrated its impact on viral replication complex assembly. However, the precise mechanisms by which DCV impairs the replication complex assembly remains elusive. In this study, by using HCV subgenomic replicons and a viral replicase assembly surrogate system in which the HCV NS3-5B polyprotein is expressed to mimic the viral replicase assembly, we assessed the impact of DCV on the aggregation and tertiary structure of NS5A, the protein-protein interactions within the viral replicase and the quaternary structure of the viral replicase...
December 5, 2018: Journal of General Virology
Allison M Rabon, Kayla L Goolsby, Michael C Young
Self-assembly of metal-organic coordination polymers occurs because of enthalpically favorable interactions. In the case of the bulky 4,4'-(anthracene-9,10-diyl)dibenzoic acid ligand (abdH2 ), we demonstrate that the presence of numerous π-π and C-H...π interactions outweigh the formation of saturated coordination complexes with zinc, leading to the formation of a dimethylformamide (DMF) solvate, namely 4,4'-(anthracene-9,10-diyl)dibenzoic acid dimethylformamide disolvate, C28 H18 O4 ·2C3 H7 NO or [(abdH2 )(DMF)2 ], at low concentrations of zinc...
December 1, 2018: Acta Crystallographica. Section C, Structural Chemistry
Swati Parbhakar, Reetam Kaushik, Firasat Hussain
A series of 12 inorganic-organic hybrid 4f-substituted arsenotungstates decorated with 3d-based complexes along with acetate bridging, viz. {[Cu2 (H2 O)(1,10-phen)2 (μ-CH3 COO)2 ]4 [Ln2 (H2 O)2 (μ-CH3 COO)2 (α-AsW11 O39 )2 ]}2- (LnIII = Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu), have been synthesized. These compounds were isolated using a one-pot synthetic strategy with copper, lanthanoid, trilacunary arsenotungstate and 1,10-phenanthroline as precursors. They were characterized using various analytical techniques, such as single-crystal X-ray diffraction (SC-XRD), powder XRD (PXRD), Fourier transform IR (FT-IR) spectroscopy, UV-Vis spectroscopy and thermogravimetric analysis (TGA)...
December 1, 2018: Acta Crystallographica. Section C, Structural Chemistry
Wesley H Brooks
The "X chromosome-nucleolus nexus" hypothesis provides a comprehensive explanation of how autoantibodies can develop following cellular stress. The hypothesis connects autoimmune diseases with the impact of environmental factors, such as viruses, through epigenetic disruption. The inactive X chromosome, a major epigenetic structure in the female cell's nucleus, is a key component of the hypothesis. The inactive X is vulnerable to disruption due to the following: (1) its heavy requirements for methylation to suppress gene expression, (2) its peripheral location at the nuclear envelope, (3) its late replication timing, and (4) its frequently observed close association with the nucleolus...
December 4, 2018: Immunologic Research
Shanshan Liu, Zhaoliang Guo, Xiongfeng Zeng, Xianguang Meng, Haina Sun, Yizao Wan, Guifu Zuo
The original version of this article unfortunately contained a mistake. In the Abstract section the sentence "Furthermore, the drug release mechanism was investigated by kinetic models and a first-order relationship was concluded, which indicated that the drug release is a simple diffusion process cohydroxyapatite/methotrexate complexntrolled by gradient drug concentration." was wrong. It should read as "Furthermore, the drug release mechanism was investigated by kinetic models and a first-order relationship was concluded, which indicated that the drug release is a simple diffusion process controlled by gradient drug concentration...
December 4, 2018: Journal of Materials Science. Materials in Medicine
Thomas Seeholzer, Susanne Kurz, Florian Schlauderer, Simone Woods, Torben Gehring, Simon Widmann, Katja Lammens, Daniel Krappmann
Assembly of the CARD11/CARMA1-BCL10-MALT1 (CBM) signaling complex upon T or B cell antigen receptor (TCR or BCR) engagement drives lymphocyte activation. Recruitment of pre-assembled BCL10-MALT1 complexes to CARD11 fosters activation of the MALT1 protease and canonical NF- κ B signaling. Structural data and in vitro assays have suggested that CARD11 acts as a seed that nucleates the assembly of BCL10 filaments, but the relevance of these findings for CBM complex assembly in cells remains unresolved. To uncouple cellular CARD11 recruitment of BCL10 and BCL10 filament assembly, we generated a BCL10-CARD11 fusion protein that links the C-terminus of BCL10 to the N-terminus of CARD11...
2018: Frontiers in Immunology
Lin Cao, Ran Zhang, Tingting Liu, Zixian Sun, Mingxu Hu, Yuna Sun, Lingpeng Cheng, Yu Guo, Sheng Fu, Junjie Hu, Xiangmin Li, Chengqi Yu, Hanyang Wang, Huanchun Chen, Xueming Li, Elizabeth E Fry, David I Stuart, Ping Qian, Zhiyong Lou, Zihe Rao
Seneca Valley virus (SVV) is an oncolytic picornavirus with selective tropism for neuroendocrine cancers. SVV mediates cell entry by attachment to the receptor anthrax toxin receptor 1 (ANTXR1). Here we determine atomic structures of mature SVV particles alone and in complex with ANTXR1 in both neutral and acidic conditions, as well as empty "spent" particles in complex with ANTXR1 in acidic conditions by cryoelectron microscopy. SVV engages ANTXR1 mainly by the VP2 DF and VP1 CD loops, leading to structural changes in the VP1 GH loop and VP3 GH loop, which attenuate interprotomer interactions and destabilize the capsid assembly...
December 4, 2018: Proceedings of the National Academy of Sciences of the United States of America
Deanna L Benson, Bridget A Matikainen-Ankney, Ayan Hussein, George W Huntley
LRRK2 mutation is the most common inherited, autosomal dominant cause of Parkinson's disease (PD) and has also been observed in sporadic cases. Most mutations result in increased LRRK2 kinase activity. LRRK2 is highly expressed in brain regions that receive dense, convergent innervation by dopaminergic and glutamatergic axons, and its levels rise developmentally coincident with glutamatergic synapse formation. The onset and timing of expression suggests strongly that LRRK2 regulates the development, maturation and function of synapses...
December 4, 2018: Biochemical Society Transactions
Roubina Tatavosian, Samantha Kent, Kyle Brown, Tingting Yao, Huy Nguyen Duc, Thao Ngoc Huynh, Chao Yu Zhen, Brian Ma, Haobin Wang, Xiaojun Ren
Polycomb group (PcG) proteins repress master regulators of development and differentiation through organization of chromatin structure. Mutation and dysregulation of PcG genes cause developmental defects and cancer. PcG proteins form condensates in the cell nucleus, and these condensates are the physical sites of PcG-targeted gene silencing via formation of facultative heterochromatin. However, the physiochemical principles underlying the formation of PcG condensates remain unknown, and their determination could shed light on how these condensates compact chromatin...
December 4, 2018: Journal of Biological Chemistry
Jian Li, Kristen Kolberg, Ulrich Schlecht, Robert P St Onge, Ana Maria Aparicio, Joe Horecka, Ronald W Davis, Maureen E Hillenmeyer, Colin Jb Harvey
Multidrug resistance is highly conserved in mammalian, fungal, and bacterial cells, is characterized by resistance to several unrelated xenobiotics, and poses significant challenges to managing infections and many cancers. Eukaryotes use a highly conserved set of drug efflux transporters that confer pleiotropic drug resistance (PDR). To interrogate the regulation of this critical process, here we developed a small molecule-responsive biosensor that couples transcriptional induction of PDR genes to growth rate in the yeast Saccharomyces cerevisiae...
December 4, 2018: Journal of Biological Chemistry
Marie Lork, Jens Staal, Rudi Beyaert
Antigen receptor-induced signaling plays an important role in inflammation and immunity. Formation of a CARD11-BCL10-MALT1 (CBM) signaling complex is a key event in T- and B cell receptor-induced gene expression by regulating NF-κB activation and mRNA stability. Deregulated CARD11, BCL10 or MALT1 expression or CBM signaling have been associated with immunodeficiency, autoimmunity and cancer, indicating that CBM formation and function have to be tightly regulated. Over the past years great progress has been made in deciphering the molecular mechanisms of assembly and disassembly of the CBM complex...
November 9, 2018: Cellular Immunology
Manoël Prouteau, Robbie Loewith
Metabolism is the sum of the life-giving chemical processes that occur within a cell. Proper regulation of these processes is essential for all organisms to thrive and prosper. When external factors are too extreme, or if internal regulation is corrupted through genetic or epigenetic changes, metabolic homeostasis is no longer achievable and diseases such as metabolic syndrome or cancer, aging, and, ultimately, death ensue. Metabolic reactions are catalyzed by proteins, and the in vitro kinetic properties of these enzymes have been studied by biochemists for many decades...
December 3, 2018: Biomolecules
Junbo He, Hao Shi, Shuangshuang Huang, Lijuan Han, Weinong Zhang, Qixin Zhong
Nanoencapsulation of α-tocopherol (α-TOC) by blending sodium oleate (NaOl) and rebaudioside A (RebA) was successfully prepared by self-assembly method under mild conditions. The optimized nanoemulsion showed the loading capacity of α-TOC was 30 wt% of sodium oleate. FTIR analysis suggested that hydrogen bonds and hydrophobic interactions were the major forces in α-TOC-NaOl/RebA complexes that were spherical and possessed well-distinguishable core-shell structures. The freeze-dried α-TOC-NaOl/RebA complexes had great stability under ambient conditions...
December 3, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Baoyan Wu, Shihua Hou, Yongyong Xue, Zhan Chen
The study reports a facile and eco-friendly approach for nanomaterial synthesis and enzyme immobilization. A corresponding glucose biosensor was fabricated by immobilizing the gold nanoparticles (AuNPs) and glucose oxidase (GOD) multilayer films onto the polypyrrole (PPy)/reduced graphene oxide (RGO) modified glassy carbon electrode (GCE) via the electrodeposition and self-assembly. PPy and graphene oxide were first coated on the surface of a bare GCE by the electrodeposition. Then, AuNPs and GOD were alternately immobilized onto PPy-RGO/GCE electrode using the electrodeposition of AuNPs and self-assembly of GOD to obtain AuNPs-GOD multilayer films...
December 1, 2018: Nanomaterials
Boris Simonetti, Peter J Cullen
Retromer is a master regulator of endosomal cargo sorting. Using cryo-EM, a new study now reveals how, in yeast, this multiprotein complex is assembled on tubular membranes to form a coat complex that orchestrates the process of tubular-based cargo sorting.
December 3, 2018: Current Biology: CB
Mengxi Liu, Shichao Li, Jingyuan Zhou, Zeqi Zha, Jinliang Pan, Xin Li, Jin Zhang, Zhongfan Liu, Yuanchang Li, Xiaohui Qiu
Rationally designed halogenated hydrocarbons are widely used building blocks to fabricate covalent-bonded carbon nanostructures on surface through a reaction pathway involving generation and dissociation of organometallic intermediates and irreversible covalent bond formation. Here we provide a comprehensive picture of the on-surface-assisted homocoupling reaction of 1,3-bis(2-bromoethynyl)benzene on Au(111), aiming for the synthesis of graphdiyne nanostructures. Submolecular resolution scanning tunneling microscopy and noncontact atomic force microscopy observations identify the organometallic intermediates and their self-assemblies formed in the dehalogenation process...
December 4, 2018: ACS Nano
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