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https://www.readbyqxmd.com/read/29781190/in-situ-study-of-the-functions-of-bacterioruberin-in-the-dual-chromophore-photoreceptor-archaerhodopsin-4
#1
Chao Sun, Xiaoyan Ding, Haolin Cui, Yanan Yang, Sijin Chen, Anthony Watts, Xin Zhao
While certain archaeal ion pumps have been shown to contain two chromophores, retinal and carotenoid bacterioruberin, the functions of the bacterioruberin have not been well explored. To address this research gap, the recombinant archaerhodopsin-4 (aR4), either with retinal chromophore only or with both retinal and bacterioruberin chromophores, was successfully expressed together with endogenous lipids in H. salinarum L33 and MPK409 respectively. In situ solid-state NMR, supported by molecular spectroscopy and functional assays, revealed for the first time that the retinal thermal equilibrium in the dark-adapted state is modulated by bacterioruberin binding via a cluster of aromatic residues on helix E...
May 20, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29780486/glucose-nucleobase-pairs-within-dna-impact-of-hydrophobicity-alternative-linking-unit-and-dna-polymerase-nucleotide-insertion-studies
#2
Empar Vengut-Climent, Pablo Peñalver, Ricardo Lucas, Irene Gómez-Pinto, Anna Aviñó, Alicia M Muro-Pastor, Elsa Galbis, M Violante de Paz, Célia Fonseca Guerra, F Matthias Bickelhaupt, Ramón Eritja, Carlos González, Juan Carlos Morales
Recently, we studied glucose-nucleobase pairs, a binding motif found in aminoglycoside-RNA recognition. DNA duplexes with glucose as a nucleobase were able to hybridize and were selective for purines. They were less stable than natural DNA but still fit well on regular B-DNA. These results opened up the possible use of glucose as a non-aromatic DNA base mimic. Here, we have studied the incorporation and thermal stability of glucose with different types of anchoring units and alternative apolar sugar-nucleobase pairs...
April 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29777720/regulation-of-shigella-effector-kinase-ospg-through-modulation-of-its-dynamic-properties
#3
Andrey M Grishin, Kathryn R Barber, Ruo-Xu Gu, D Peter Tieleman, Gary S Shaw, Miroslaw Cygler
Gram-negative pathogens secrete effector proteins into human cells to modulate normal cellular processes and establish a bacterial replication niche. Shigella and pathogenic E. coli possess homologous effector kinases, OspG and NleH1/2, respectively. Upon translocation, OspG but not NleH binds to ubiquitin and a subset of E2~Ub conjugates, which was shown to activate its kinase activity. Here we show that OspG, having a minimal kinase fold, acquired a novel mechanism of regulation of its activity. Binding of the E2~Ub conjugate to OspG not only stimulates its kinase activity but also increases its optimal temperature for activity to match the human body temperature and stabilizes its labile C-terminal domain...
May 16, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29775281/highly-stretchable-waterproof-fiber-asymmetric-supercapacitors-in-an-integrated-structure
#4
Kai Guo, Xianfu Wang, Lintong Hu, Tianyou Zhai, Huiqiao Li, Neng Yu
Fiber supercapacitors have attracted tremendous attention as promising power source candidates for next generation of wearable electronics, which are flexible, stretchable, and washable. Although asymmetric fiber supercapacitors with a high energy density have been achieved, their stretchability is no more than 200%, and they still face mechanical instability and unreliable waterproof structure. This work develops a highly integrated structure for waterproof, highly stretchable and asymmetric fiber-shaped supercapacitor, which is assembled by integrating a helix-shaped asymmetric fiber supercapacitor into a bifunctional polymer...
May 18, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29768206/intrinsic-instability-of-bok-enables-membrane-permeabilization-in-apoptosis
#5
Janet H Zheng, Christy R Grace, Cristina D Guibao, Dan E McNamara, Fabien Llambi, Yue-Ming Wang, Taosheng Chen, Tudor Moldoveanu
The effector B cell lymphoma-2 (BCL-2) protein BCL-2 ovarian killer (BOK) induces mitochondrial outer membrane permeabilization (MOMP) to initiate apoptosis upon inhibition of the proteasome. How BOK mediates MOMP is mechanistically unknown. The NMR structure of the BCL-2 core of human BOK reveals a conserved architecture with an atypical hydrophobic groove that undergoes conformational exchange. Remarkably, the BCL-2 core of BOK spontaneously associates with purified mitochondria to release cytochrome c in MOMP assays...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29768204/an-amphipathic-helix-directs-cellular-membrane-curvature-sensing-and-function-of-the-bar-domain-protein-pick1
#6
Rasmus Herlo, Viktor K Lund, Matthew D Lycas, Anna M Jansen, George Khelashvili, Rita C Andersen, Vikram Bhatia, Thomas S Pedersen, Pedro B C Albornoz, Niklaus Johner, Ina Ammendrup-Johnsen, Nikolaj R Christensen, Simon Erlendsson, Mikkel Stoklund, Jannik B Larsen, Harel Weinstein, Ole Kjærulff, Dimitrios Stamou, Ulrik Gether, Kenneth L Madsen
BAR domains are dimeric protein modules that sense, induce, and stabilize lipid membrane curvature. Here, we show that membrane curvature sensing (MCS) directs cellular localization and function of the BAR domain protein PICK1. In PICK1, and the homologous proteins ICA69 and arfaptin2, we identify an amphipathic helix N-terminal to the BAR domain that mediates MCS. Mutational disruption of the helix in PICK1 impaired MCS without affecting membrane binding per se. In insulin-producing INS-1E cells, super-resolution microscopy revealed that disruption of the helix selectively compromised PICK1 density on insulin granules of high curvature during their maturation...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29763333/linker-directed-assembly-of-twisted-ortho-phenylene-based-macrocycles
#7
Zacharias J Kinney, C Scott Hartley
o-Phenylene tetramers have been coassembled with linkers into macrocycles through imine condensation. Variation of linker connectivity and length allows both [1 + 1] and [2 + 2] macrocycles to be obtained, complementing (previously reported) [3 + 3] macrocycles. For the [1 + 1] macrocycles, linker length has a clear effect on o-phenylene geometry and macrocycle stability. For the [2 + 2] macrocycles, both homo- and heterochiral configurations are observed, suggesting limited communication of helix handedness in these systems...
May 15, 2018: Organic Letters
https://www.readbyqxmd.com/read/29760086/mapping-the-functional-anatomy-of-orai1-transmembrane-domains-for-crac-channel-gating
#8
Priscilla S-W Yeung, Megumi Yamashita, Christopher E Ing, Régis Pomès, Douglas M Freymann, Murali Prakriya
Store-operated Orai1 channels are activated through a unique inside-out mechanism involving binding of the endoplasmic reticulum Ca2+ sensor STIM1 to cytoplasmic sites on Orai1. Although atomic-level details of Orai structure, including the pore and putative ligand binding domains, are resolved, how the gating signal is communicated to the pore and opens the gate is unknown. To address this issue, we used scanning mutagenesis to identify 15 residues in transmembrane domains (TMs) 1-4 whose perturbation activates Orai1 channels independently of STIM1...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29760064/helical-rotation-of-the-diaphanous-related-formin-mdia1-generates-actin-filaments-resistant-to-cofilin
#9
Hiroaki Mizuno, Kotaro Tanaka, Sawako Yamashiro, Akihiro Narita, Naoki Watanabe
The complex interplay between actin regulatory proteins facilitates the formation of diverse cellular actin structures. Formin homology proteins (formins) play an essential role in the formation of actin stress fibers and yeast actin cables, to which the major actin depolymerizing factor cofilin barely associates. In vitro, F-actin decorated with cofilin exhibits a marked increase in the filament twist. On the other hand, a mammalian formin mDia1 rotates along the long-pitch actin helix during processive actin elongation (helical rotation)...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29758270/collagen-gly-missense-mutations-effect-of-residue-identity-on-collagen-structure-and-integrin-binding
#10
Yimin Qiu, Arya Mekkat, Hongtao Yu, Sezin Yigit, Samir Hamaia, Richard W Farndale, David L Kaplan, Yu-Shan Lin, Barbara Brodsky
Gly missense mutations in type I collagen, which replace a conserved Gly in the repeating (Gly-Xaa-Yaa)n sequence with a larger residue, are known to cause Osteogenesis Imperfecta (OI). The clinical consequences of such mutations range from mild to lethal, with more serious clinical severity associated with larger Gly replacement residues. Here, we investigate the influence of the identity of the residue replacing Gly within and adjacent to the integrin binding 502 GFPGER507 sequence on triple-helix structure, stability and integrin binding using a recombinant bacterial collagen system...
May 11, 2018: Journal of Structural Biology
https://www.readbyqxmd.com/read/29758269/g-quadruplex-in-animal-development-contribution-to-gene-expression-and-genomic-heterogeneity
#11
REVIEW
Pablo Armas, Nora Beatriz Calcaterra
During animal development, gene expression is orchestrated by specific and highly evolutionarily conserved mechanisms that take place accurately, both at spatial and temporal levels. The last decades have provided compelling evidence showing that chromatin state plays essential roles in orchestrating most of the stages of development. The DNA molecule can adopt alternative structures different from the helical duplex architecture. G-rich DNA sequences can fold as intrastrand quadruple helix structures called G-quadruplexes or G4-DNA...
May 11, 2018: Mechanisms of Development
https://www.readbyqxmd.com/read/29754825/structure-of-human-nata-and-its-regulation-by-the-huntingtin-interacting-protein-hypk
#12
Leah Gottlieb, Ronen Marmorstein
Co-translational N-terminal protein acetylation regulates many protein functions including degradation, folding, interprotein interactions, and targeting. Human NatA (hNatA), one of six conserved metazoan N-terminal acetyltransferases, contains Naa10 catalytic and Naa15 auxiliary subunits, and associates with the intrinsically disordered Huntingtin yeast two-hybrid protein K (HYPK). We report on the crystal structures of hNatA and hNatA/HYPK, and associated biochemical and enzymatic analyses. We demonstrate that hNatA contains unique features: a stabilizing inositol hexaphosphate (IP6 ) molecule and a metazoan-specific Naa15 domain that mediates high-affinity HYPK binding...
April 23, 2018: Structure
https://www.readbyqxmd.com/read/29751951/biochemical-characterization-and-immunogenicity-of-neureight-a-recombinant-full-length-factor-viii-produced-by-fed-batch-process-in-disposable-bioreactors
#13
Sandrine Delignat, Ivan Peyron, Maria El Ghazaly, Srinivas V Kaveri, Jan Rohde, Frank Mueller, Sebastien Lacroix-Desmazes
Hemophilia A is a X-linked recessive bleeding disorder consecutive to the lack of circulating pro-coagulant factor VIII (FVIII). The most efficient strategy to treat or prevent bleeding in patients with hemophilia A relies on replacement therapy using exogenous FVIII. Commercially available recombinant FVIII are produced using an expensive perfusion technology in stainless steel fermenters. A fed-batch fermentation technology was recently developed to produce 'Neureight', a full-length recombinant human FVIII, in Chinese hamster ovary (CHO) cells...
May 5, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29750782/hey1-and-p53-dependent-trkc-proapoptotic-activity-controls-neuroblastoma-growth
#14
Marie Ménard, Clélia Costechareyre, Gabriel Ichim, Jonathan Blachier, David Neves, Loraine Jarrosson-Wuilleme, Reinhard Depping, Jan Koster, Pierre Saintigny, Patrick Mehlen, Servane Tauszig-Delamasure
The neurotrophin-3 (NT-3) receptor tropomyosin receptor kinase C (TrkC/NTRK3) has been described as a dependence receptor and, as such, triggers apoptosis in the absence of its ligand NT-3. This proapoptotic activity has been proposed to confer a tumor suppressor activity to this classic tyrosine kinase receptor (RTK). By investigating interacting partners that might facilitate TrkC-induced cell death, we have identified the basic helix-loop-helix (bHLH) transcription factor Hey1 and importin-α3 (karyopherin alpha 4 [KPNA4]) as direct interactors of TrkC intracellular domain, and we show that Hey1 is required for TrkC-induced apoptosis...
May 11, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29745668/temperature-induced-self-assembly-of-the-group-b-streptococcus-gbs-fusion-antigen-gbs-nn
#15
Fabrice Rose, Silke Roovers, Mathias Fanø, Stine Harloff-Helleberg, Jacob Judas Kain Kirkensgaard, Kim Hejnaes, Per Fischer, Camilla Foged
Group B streptococcus (GBS) is a leading cause of serious bacterial neonatal infections worldwide, which provides an unmet medical need for a globally effective vaccine. The recombinant GBS fusion antigen GBS-NN contains the N-terminal regions of the GBS Rib and Alpha C proteins. It shows promising immunogenicity eliciting protective immunity in mice and encouraging results in early human clinical trials. Understanding the physical stability of GBS-NN containing conformational B-cell epitopes is crucial to ensure optimal vaccine stability, efficacy and safety...
May 10, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29745554/-study-on-biological-characteristics-and-stability-of-the-linear-derivative-bac2a-from-bactenecin
#16
Yingying Li, Wanjun Han, Songsong Cao, Juncai Hou, Zhanmei Jiang, Chenggang Jiang, Haimei Wang, Shiyue Pang
The objective of the study is to analyze the biological characteristics and stability of the linear derivative Bac2a from bactenecin, compared with the control peptide melittin. The secondary structure, antibacterial activity, hemolytic activity, cell toxicity and stability of the Bac2a were determined by circular dichroism spectroscopy, broth micro-dilution method and MTT assay. The results showed that Bac2a was a nonregular curl in aqueous solution, however, it was an α-helix structure in the hydrophobic environment...
August 1, 2017: Sheng Wu Yi Xue Gong Cheng Xue za Zhi, Journal of Biomedical Engineering, Shengwu Yixue Gongchengxue Zazhi
https://www.readbyqxmd.com/read/29742459/amino-acid-content-of-beta-strands-and-alpha-helices-depends-on-their-flanking-secondary-structure-elements
#17
Vladislav Victorovich Khrustalev, Tatyana Aleksandrovna Khrustaleva, Victor Vitoldovich Poboinev
The influence of flanking structures (alpha helices and beta strands in the primary sequence) on amino acid content of the elements of secondary structure has been analyzed in seven sets of nonhomologous proteins. Elevated usage of beta structural amino acid residues and pentapeptides in beta strands between two alpha helices can be explained by the stabilization of secondary structure of those beta strands by natural selection. High usage of alpha helical amino acids and pentapeptides in beta strands situated between two other beta strands is an evidence of the relaxation of natural selection: "passive" beta strands in these fragments of polypeptide chains are frequently formed due to the influence of flanking "active" beta strands...
May 6, 2018: Bio Systems
https://www.readbyqxmd.com/read/29740459/3d-structures-of-plant-phytochrome-a-as-pr-and-pfr-from-solid-state-nmr-implications-for-molecular-function
#18
Chen Song, Maria Andrea Mroginski, Christina Lang, Jakub Kopycki, Wolfgang Gärtner, Jörg Matysik, Jon Hughes
We present structural information for oat phyA3 in the far-red-light-absorbing (Pfr) signaling state, to our knowledge the first three-dimensional (3D) information for a plant phytochrome as Pfr. Solid-state magic-angle spinning (MAS) NMR was used to detect interatomic contacts in the complete photosensory module [residues 1-595, including the NTE (N-terminal extension), PAS ( P er/ A rnt/ S im), GAF (c G MP phosphodiesterase/ a denylyl cyclase/ F hlA) and PHY ( phy tochrome-specific) domains but with the C-terminal PAS repeat and transmitter-like module deleted] auto-assembled in vitro with 13 C- and 15 N-labeled phycocyanobilin (PCB) chromophore...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29739880/ccr5-adopts-three-homodimeric-conformations-that-control-cell-surface-delivery
#19
Jun Jin, Fanny Momboisse, Gaelle Boncompain, Florian Koensgen, Zhicheng Zhou, Nelia Cordeiro, Fernando Arenzana-Seisdedos, Franck Perez, Bernard Lagane, Esther Kellenberger, Anne Brelot
Biophysical methods and x-ray crystallography have revealed that class A G protein-coupled receptors (GPCRs) can form homodimers. We combined computational approaches with receptor cross-linking, energy transfer, and a newly developed functional export assay to characterize the residues involved in the dimerization interfaces of the chemokine receptor CCR5, the major co-receptor for HIV-1 entry into cells. We provide evidence of three distinct CCR5 dimeric organizations, involving residues of transmembrane helix 5...
May 8, 2018: Science Signaling
https://www.readbyqxmd.com/read/29733023/identification-and-bioactivity-analysis-of-a-newly-identified-defensin-from-the-oyster-magallana-gigas
#20
Yubo Zhang, Pengfei Cui, Yashuo Wang, Shicui Zhang
The relatively conserved sequences of signal peptides and proregions that antimicrobial peptides (AMPs) contain have been successfully used to search for and identify novel AMPs from databases within the same lineages of fish and amphibians and across different animal classes. If such an approach is applicable to invertebrate species such as oyster has not yet been tested so far. In this study, we found a cDNA from the digestive gland of the oyster Magallana gigas, designated Mgdefdg, which contains two exons interspaced by one intron...
August 2018: Developmental and Comparative Immunology
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