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Journal of Molecular Biology

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https://www.readbyqxmd.com/read/30641082/n-glycan-utilization-by-bifidobacterium-gut-symbionts-involves-a-specialist-%C3%AE-mannosidase
#1
Rosa Lorizolla Cordeiro, Renan Augusto Siqueira Pirolla, Gabriela Felix Persinoti, Fábio Cesar Gozzo, Priscila Oliveira de Giuseppe, Mario Tyago Murakami
Bifidobacteria represent one of the first colonizers of human gut microbiota, providing to this ecosystem better health and nutrition. To maintain a mutualistic relationship, they have enzymes to degrade and use complex carbohydrates non-digestible by their hosts. To succeed in the densely populated gut environment, they evolved molecular strategies that remain poorly understood. Herein, we report a novel mechanism found in probiotic Bifidobacteria for the depolymerization of the ubiquitous Man-β-1,4-GlcNAc, a disaccharide that composes the universal core of eukaryotic N-glycans...
January 11, 2019: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30639410/nmr-investigation-of-the-interaction-between-the-recq-c-terminal-domain-of-human-bloom-syndrome-protein-and-g-quadruplex-dna-from-the-human-c-myc-promoter
#2
Sungjin Lee, Ae-Ree Lee, Kyoung-Seok Ryu, Joon-Hwa Lee, Chin-Ju Park
Bloom syndrome protein (BLM) is one of five human RecQ helicases that participate in DNA metabolism. RecQ C-terminal (RQC) domain is the main DNA binding module of BLM and specifically recognizes G-quadruplex (G4) DNA structures. Because G4 processing by BLM is essential for regulating replication and transcription, both G4 and BLM are considered as potential targets for anticancer therapy. Although several studies have revealed the detailed mechanism of G4 unwinding by BLM, the initial recognition of the G4 structure by the RQC domain is unclear...
January 10, 2019: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30639409/the-role-of-connexins-in-gastrointestinal-diseases
#3
REVIEW
Jeremy Wong, Jasmine Chopra, Lorraine Lok Wing Chiang, Tong Liu, Jeffery Ho, William K K Wu, Gary Tse, Sunny Hei Wong
Gap junctions are hexagonal arrays of protein molecules in the plasma membrane and were first described in Mauthner cell synapses of goldfish. They form pathways for coupling between cells, allowing passive, electrotonic spread of ions and also passage of larger molecules such as amino acids and nucleotides. They are expressed in both excitable and non-excitable tissues. Each gap junction is made of two connexons, which are hexameric proteins of the connexin subunit. In this review, the roles that connexins play in GI motility, the mechanisms of altered connexin expression leading to inflammatory bowel disease, gastrointestinal infections and gastrointestinal symptoms in autistic spectrum disorder are discussed in detail...
January 10, 2019: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30639408/crystal-structures-of-csm2-and-csm3-in-the-type-iii-a-crispr-cas-effector-complex
#4
Daijiro Takeshita, Momoe Sato, Hideko Inanaga, Tomoyuki Numata
Clustered regularly interspaced short palindromic repeat (CRISPR) loci and CRISPR-associated (Cas) genes encode CRISPR RNAs (crRNA) and Cas proteins, respectively, which play important roles in the adaptive immunity system (CRISPR-Cas system) in prokaryotes. The crRNA and Cas proteins form ribonucleoprotein effector complexes to capture and degrade invading genetic materials with base complementarity to the crRNA guide sequences. The Csm complex, a type III-A effector complex, comprises five Cas proteins (Csm1-Csm5) and a crRNA, which co-transcriptionally degrades invading DNA and RNA...
January 10, 2019: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30639189/untying-a-protein-knot-by-circular-permutation
#5
Ya-Chu Chuang, I-Chen Hu, Ping-Chiang Lyu, Shang-Te Danny Hsu
Topologically knotted proteins are tantalizing examples of how polypeptide chains can explore complex free energy landscapes to efficiently attain defined knotted conformations. The evolution trails of protein knots, however, remain elusive. We used circular permutation to change an evolutionally conserved topologically knotted SPOUT RNA methyltransferase into an unknotted form. The unknotted variant adopted the same three-dimensional structure and oligomeric state as its knotted parent but its folding stability was markedly reduced with accelerated folding kinetics and its ligand binding was abrogated...
January 9, 2019: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30639188/acetylation-of-response-regulator-proteins-tcrx-and-mtra-in-m-tuberculosis-tunes-their-phosphotransfer-ability-and-modulates-two-component-signaling-crosstalk
#6
Krishna Kumar Singh, Neerupma Bhardwaj, Gaurav D Sankhe, Niveda Udaykumar, Rambir Singh, Vandana Malhotra, Deepak Kumar Saini
Two-component signal transduction (TCS) cascades involve stimulus-dependent activation and phosphorylation of a sensor kinase (SK), which then transfers the phosphoryl moiety to the response regulator (RR) protein. The fidelity of this phosphotransfer reaction from the SK to the RR provides specificity to TCS signaling. In the present study, we show that for TcrX, a transcriptionally autoregulated RR of M. tuberculosis, acetylation enhances its net phosphorylation from cognate SK TcrY and lowers it from a non-cognate SK MtrB...
January 9, 2019: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30639187/new-insights-into-amino-terminal-translocation-as-revealed-by-the-use-of-yidc-and-sec-depletion-strains
#7
Sri Karthika Shanmugam, Nicholas Backes, Yuanyuan Chen, Alexandra Belardo, Gregory J Phillips, Ross E Dalbey
Different attributes of membrane protein substrates have been proposed and characterized as translocation-pathway determinants. However, several gaps in our understanding of the mechanism of targeting, insertion and assembly of inner membrane proteins exist. Specifically, the role played by hydrophilic N-terminal tails in pathway selection is unclear. In this study we have evaluated length and charge density as translocase determinants using model proteins. Strikingly, the 36 residue N-tail of 2Pf3-Lep translocates independent of YidC-Sec...
January 9, 2019: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30633872/divalent-cations-alter-the-rate-limiting-step-of-primpol-catalyzed-dna-elongation
#8
Wenyan Xu, Wenxin Zhao, Nana Morehouse, Maya O Tree, Linlin Zhao
PrimPol is the most recently discovered human DNA polymerase/primase and plays an emerging role in nuclear and mitochondrial genomic maintenance. As a member of archaeo-eukaryotic primase (AEP) superfamily enzymes, PrimPol possesses DNA polymerase and primase activities that are important for replication fork progression in vitro and in cellulo. The enzymatic activities of PrimPol are critically dependent on the nucleotidyl-transfer reaction to incorporate deoxyribonucleotides successively; however, our knowledge concerning the kinetic mechanism of the reaction remains incomplete...
January 8, 2019: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30633871/the-bacterial-chromatin-protein-hupa-can-remodel-dna-and-associates-with-the-nucleoid-in-clostridium-difficile
#9
Ana M Oliveira Paiva, Annemieke H Friggen, Liang Qin, Roxanne Douwes, Remus T Dame, Wiep Klaas Smits
The maintenance and organization of the chromosome plays an important role in the development and survival of bacteria. Bacterial chromatin proteins are architectural proteins that bind DNA, modulate its conformation and by doing so affect a variety of cellular processes. No bacterial chromatin proteins of C. difficile have been characterized to date. Here, we investigate aspects of the C. difficile HupA protein, a homolog of the histone-like HU proteins of Escherichia coli. HupA is a 10 kDa protein that is present as a homodimer in vitro and self-interacts in vivo...
January 8, 2019: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30630008/rna-polymerase-clamp-movement-aids-dissociation-from-dna-but-is-not-required-for-rna-release-at-intrinsic-terminators
#10
Michael J Bellecourt, Ananya Ray-Soni, Alex Harwig, Rachel Anne Mooney, Robert Landick
In bacteria, disassembly of elongating transcription complexes (ECs) can occur at intrinsic terminators in a 2-3 nucleotide window after transcription of multiple kilobase pairs of DNA. Intrinsic terminators trigger pausing on weak RNA-DNA hybrids followed by formation of a strong, GC-rich stem-loop in the RNA exit channel of RNA polymerase (RNAP), inactivating nucleotide addition and inducing dissociation of RNA and RNAP from DNA. Although the movements of RNA and DNA during intrinsic termination have been studied extensively leading to multiple models, the effects of RNAP conformational changes remain less well-defined...
January 7, 2019: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30625288/changing-the-apoptosis-pathway-through-evolutionary-protein-design
#11
David Shultis, Pralay Mitra, Xiaoqiang Huang, Jarrett Johnson, Naureen Aslam Khattak, Felicia Gray, Clint Piper, Jeff Czajka, Logan Hansen, Bingbing Wan, Krishnapriya Chinnaswamy, Liu Liu, Mi Wang, Jingxi Pan, Jeanne Stuckey, Tomasz Cierpicki, Christoph H Borchers, Shaomeng Wang, Ming Lei, Yang Zhang
One obstacle in de novo protein design is the vast sequence space that needs to be searched through to obtain functional proteins. We developed a new method using structural profiles created from evolutionarily related proteins to constrain the simulation search process, with functions specified by atomic-level ligand-protein binding interactions. The approach was applied to redesigning the BIR3 domain of the X-linked inhibitor of apoptosis protein (XIAP), whose primary function is to suppress the cell death by inhibiting caspase-9 activity; however, the function of the wild-type XIAP can be eliminated by the binding of Smac peptides...
January 6, 2019: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30611750/peptide-design-principles-for-antimicrobial-applications
#12
REVIEW
Marcelo D T Torres, Shanmugapriya Sothiselvam, Timothy K Lu, Cesar de la Fuente-Nunez
The increased incidence of bacterial resistance to available antibiotics represents a major global health problem and highlights the need for novel anti-infective therapies. Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics. AMPs are versatile, have almost unlimited sequence space, and can be tuned for broad-spectrum or specific activity against microorganisms. However, several obstacles remain to be overcome in order to develop AMPs for medical use, such as toxicity, stability, and bacterial resistance...
January 3, 2019: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30611749/ruggedness-in-the-free-energy-landscape-dictates-misfolding-of-the-prion-protein
#13
Roumita Moulick, Rama Reddy Goluguri, Jayant B Udgaonkar
Experimental determination of the key features of the free energy landscapes of proteins which dictate their adeptness to fold correctly, or propensity to misfold and aggregate, and which are modulated upon a change from physiological to aggregation-prone conditions, is a difficult challenge. In this study, sub-millisecond kinetic measurements of the folding and unfolding of the mouse prion protein (moPrP), reveal how the free energy landscape becomes more complex upon a shift from physiological (pH 7) to aggregation-prone (pH 4) conditions...
January 3, 2019: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30597163/fluorescent-trimeric-hemagglutinins-reveal-multivalent-receptor-binding-properties
#14
Nikoloz Nemanichvili, Ilhan Tomris, Hannah L Turner, Ryan McBride, Oliver C Grant, Roosmarijn van der Woude, Mohammed H Aldosari, Roland J Pieters, Robert J Woods, James C Paulson, Geert-Jan Boons, Andrew B Ward, Monique H Verheije, Robert P de Vries
Influenza A virus carries hundreds of trimeric hemagglutinins proteins (HA) on its viral envelope that interact with various sialylated glycans on a host cell. This interaction represents a multivalent binding event that is present in all the current receptor-binding assays, including those employing viruses or precomplexed HA trimers. To study the nature of such multivalent binding events, we fused a super folder GFP (sfGFP) to the C-terminus of trimeric HA to allow direct visualization of HA-receptor interactions without the need for additional fluorescent antibodies...
December 28, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30597162/the-biophysical-basis-for-phosphorylation-enhanced-dna-binding-autoinhibition-of-the-ets1-transcription-factor
#15
Cecilia Perez-Borrajero, Chang Sheng-Huei Lin, Mark Okon, Karlton Scheu, Barbara J Graves, Michael E P Murphy, Lawrence P McIntosh
The eukaryotic transcription factor ETS1 is regulated by an intrinsically disordered serine-rich region (SRR) that transiently associates with the adjacent ETS domain to inhibit DNA binding. In this study, we further elucidated the physicochemical basis for ETS1 autoinhibition by characterizing the interaction of its ETS domain with a series of synthetic peptides corresponding to the SRR. Binding is driven by the hydrophobic effect and enhanced electrostatically by phosphorylation of serines adjacent to aromatic residues in the amphipathic SRR...
December 28, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30597161/rna-mediated-disease-mechanisms-in-neurodegenerative-disorders
#16
REVIEW
Andreas Neueder
RNA is accurately entangled in virtually all pathways that maintain cellular homeostasis. To name but a few, RNA is the 'messenger' between DNA encoded information and the resulting proteins. Furthermore, RNAs regulate diverse processes by forming DNA::RNA or RNA::RNA interactions. Finally, RNA itself can be the scaffold for ribonucleoprotein complexes, e.g. ribosomes or cellular bodies. Consequently, disruption of any of these processes can lead to disease. This review describes known and emerging RNA based disease mechanisms like interference with regular splicing, the anomalous appearance of RNA-protein complexes and uncommon RNA species, as well as non-canonical translation...
December 28, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30597160/abcf-atpases-involved-in-protein-synthesis-ribosome-assembly-and-antibiotic-resistance-structural-and-functional-diversification-across-the-tree-of-life
#17
Victoriia Murina, Marje Kasari, Hiraku Takada, Mariliis Hinnu, Chayan Kumar Saha, James W Grimshaw, Takahiro Seki, Michael Reith, Marta Putrinš, Tanel Tenson, Henrik Strahl, Vasili Hauryliuk, Gemma Catherine Atkinson
Within the larger ABC superfamily of ATPases, ABCF family members eEF3 in Saccharomyces cerevisiae and EttA in Escherichia coli have been found to function as ribosomal translation factors. Several other ABCFs including biochemically characterised VgaA, LsaA and MsrE confer resistance to antibiotics that target the peptidyl transferase centre and exit tunnel of the ribosome. However, the diversity of ABCF subfamilies, the relationships among subfamilies and the evolution of antibiotic resistance factors from other ABCFs have not been explored...
December 28, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30580037/zinc-induces-temperature-dependent-reversible-self-assembly-of-tau
#18
Andrei Yu Roman, François Devred, Deborah Byrne, Romain La Rocca, Natalia N Ninkina, Vincent Peyrot, Philipp O Tsvetkov
Tau is an intrinsically disordered microtubule-associated protein that is implicated in several neurodegenerative disorders called Tauopathies. In these diseases, Tau is found in the form of intracellular inclusions that consist of aggregated paired helical filaments (PHFs) in neurons. Given the importance of this irreversible PHF formation in neurodegenerative disease, Tau aggregation has been extensively studied. Several different factors, such as mutations or post translational modifications, have been shown to influence the formation of late-stage non-reversible Tau aggregates...
December 20, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30580036/structural-and-biochemical-characterization-of-aldehyde-dehydrogenase-12-the-last-enzyme-of-proline-catabolism-in-plants
#19
David A Korasick, Radka Končitíková, Martina Kopečná, Eva Hájková, Armelle Vigouroux, Solange Moréra, Donald F Becker, Marek Šebela, John J Tanner, David Kopečný
Heterokonts, Alveolata protists, green algae from Charophyta and Chlorophyta divisions, and all Embryophyta plants possess an aldehyde dehydrogenase (ALDH) gene named ALDH12. Here, we provide a biochemical characterization of two ALDH12 family members from the lower plant Physcomitrella patens and higher plant Zea mays. We show ALDH12 encodes an NAD+ -dependent glutamate γ-semialdehyde dehydrogenase (GSALDH), which irreversibly converts glutamate γ-semialdehyde (GSAL), a mitochondrial intermediate of the proline and arginine catabolism, to glutamate...
December 20, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30562484/nature-of-the-pre-chemistry-ensemble-in-mitogen-activated-protein-kinases
#20
Ranajeet Ghose
In spite of the availability of a significant amount of structural detail on docking interactions involving mitogen activated protein kinases (MAPKs) and their substrates, the mechanism by which the disordered phospho-acceptor on the substrate transiently interacts with the kinase catalytic elements and is phosphorylated, often with high efficiency, remains poorly understood. In this perspective this dynamic interaction is analyzed in the context of available biophysical and biochemical data for ERK2, an archetypal MAPK...
December 15, 2018: Journal of Molecular Biology
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