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Protein resurrection

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https://www.readbyqxmd.com/read/27899133/adaptively-introgressed-neandertal-haplotype-at-the-oas-locus-functionally-impacts-innate-immune-responses-in-humans
#1
Aaron J Sams, Anne Dumaine, Yohann Nédélec, Vania Yotova, Carolina Alfieri, Jerome E Tanner, Philipp W Messer, Luis B Barreiro
BACKGROUND: The 2'-5' oligoadenylate synthetase (OAS) locus encodes for three OAS enzymes (OAS1-3) involved in innate immune response. This region harbors high amounts of Neandertal ancestry in non-African populations; yet, strong evidence of positive selection in the OAS region is still lacking. RESULTS: Here we used a broad array of selection tests in concert with neutral coalescent simulations to demonstrate a signal of adaptive introgression at the OAS locus...
November 29, 2016: Genome Biology
https://www.readbyqxmd.com/read/27863072/when-directed-evolution-met-ancestral-enzyme-resurrection
#2
Miguel Alcalde
The directed evolution of ancestral -resurrected- enzymes can give a new twist in protein engineering approaches towards more versatile and robust biocatalysts.
November 11, 2016: Microbial Biotechnology
https://www.readbyqxmd.com/read/27846568/predictable-convergence-in-hemoglobin-function-has-unpredictable-molecular-underpinnings
#3
Chandrasekhar Natarajan, Federico G Hoffmann, Roy E Weber, Angela Fago, Christopher C Witt, Jay F Storz
To investigate the predictability of genetic adaptation, we examined the molecular basis of convergence in hemoglobin function in comparisons involving 56 avian taxa that have contrasting altitudinal range limits. Convergent increases in hemoglobin-oxygen affinity were pervasive among high-altitude taxa, but few such changes were attributable to parallel amino acid substitutions at key residues. Thus, predictable changes in biochemical phenotype do not have a predictable molecular basis. Experiments involving resurrected ancestral proteins revealed that historical substitutions have context-dependent effects, indicating that possible adaptive solutions are contingent on prior history...
October 21, 2016: Science
https://www.readbyqxmd.com/read/27825296/resurrecting-ancestral-structural-dynamics-of-an-antiviral-immune-receptor-adaptive-binding-pocket-reorganization-repeatedly-shifts-rna-preference
#4
Charles Pugh, Oralia Kolaczkowski, Austin Manny, Bryan Korithoski, Bryan Kolaczkowski
BACKGROUND: Although resurrecting ancestral proteins is a powerful tool for understanding the molecular-functional evolution of gene families, nearly all studies have examined proteins functioning in relatively stable biological processes. The extent to which more dynamic systems obey the same 'rules' governing stable processes is unclear. Here we present the first detailed investigation of the functional evolution of the RIG-like receptors (RLRs), a family of innate immune receptors that detect viral RNA in the cytoplasm...
November 8, 2016: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/27623311/phosphorylation-of-blar1-in-manifestation-of-antibiotic-resistance-in-methicillin-resistant-staphylococcus-aureus-and-its-abrogation-by-small-molecules
#5
Marc A Boudreau, Jennifer Fishovitz, Leticia I Llarrull, Qiaobin Xiao, Shahriar Mobashery
Methicillin-resistant Staphylococcus aureus (MRSA), an important human pathogen, has evolved an inducible mechanism for resistance to β-lactam antibiotics. We report herein that the integral membrane protein BlaR1, the β-lactam sensor/signal transducer protein, is phosphorylated on exposure to β-lactam antibiotics. This event is critical to the onset of the induction of antibiotic resistance. Furthermore, we document that BlaR1 phosphorylation and the antibiotic-resistance phenotype are both reversed in the presence of synthetic protein kinase inhibitors of our design, restoring susceptibility of the organism to a penicillin, resurrecting it from obsolescence in treatment of these intransigent bacteria...
October 9, 2015: ACS Infectious Diseases
https://www.readbyqxmd.com/read/27600879/rational-design-and-engineering-of-a-mutant-variant-of-urate-oxidase-as-a-therapeutic-enzyme-a-molecular-dynamics-simulation-approach
#6
Sajjad Ahrari, Fatemeh Dabbagh, Sobhan Ahrari, Younes Ghasemi, Navid Mogharrab, Yasser Riazalhosseini
BACKGROUND: Urate oxidase is absent in humans so the enzyme is considered as an important therapeutic agent to control hyperuricemic disorders. Currently available enzymes with pharmaceutical applications have adverse effects associated with allergic reactions and anaphylactic shocks, in case of chronic treatment. Therefore, developing variant forms of the enzyme, with lower immunogenicity and similar or higher activity, is of great importance. AIM: Here, we tried to improve the structure of a recently resurrected ancestral mammalian urate oxidase (which is claimed to have higher enzymatic activity compared to other mammalian counterparts) by introducing eight rational mutations and verified the consequence of these mutations on immunogenicity, stability and the affinity of protein to uric acid by computational techniques...
September 5, 2016: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/27528732/engineering-ancestral-protein-hyperstability
#7
M Luisa Romero-Romero, Valeria A Risso, Sergio Martinez-Rodriguez, Beatriz Ibarra-Molero, Jose M Sanchez-Ruiz
Many experimental analyses and proposed scenarios support that ancient life was thermophilic. In congruence with this hypothesis, proteins encoded by reconstructed sequences corresponding to ancient phylogenetic nodes often display very high stability. Here, we show that such 'reconstructed ancestral hyperstability' can be further engineered on the basis of a straightforward approach that uses exclusively information afforded by the ancestral reconstruction process itself. Since evolution does not imply continuous progression, screening of the mutations between two evolutionarily related resurrected ancestral proteins may identify mutations that further stabilize the most stable one...
October 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27472806/phylobot-a-web-portal-for-automated-phylogenetics-ancestral-sequence-reconstruction-and-exploration-of-mutational-trajectories
#8
Victor Hanson-Smith, Alexander Johnson
The method of phylogenetic ancestral sequence reconstruction is a powerful approach for studying evolutionary relationships among protein sequence, structure, and function. In particular, this approach allows investigators to (1) reconstruct and "resurrect" (that is, synthesize in vivo or in vitro) extinct proteins to study how they differ from modern proteins, (2) identify key amino acid changes that, over evolutionary timescales, have altered the function of the protein, and (3) order historical events in the evolution of protein function...
July 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27403565/studying-the-supramolecular-organization-of-photosynthetic-membranes-within-freeze-fractured-leaf-tissues-by-cryo-scanning-electron-microscopy
#9
Dana Charuvi, Reinat Nevo, Ifat Kaplan-Ashiri, Eyal Shimoni, Ziv Reich
Cryo-scanning electron microscopy (SEM) of freeze-fractured samples allows investigation of biological structures at near native conditions. Here, we describe a technique for studying the supramolecular organization of photosynthetic (thylakoid) membranes within leaf samples. This is achieved by high-pressure freezing of leaf tissues, freeze-fracturing, double-layer coating and finally cryo-SEM imaging. Use of the double-layer coating method allows acquiring high magnification (>100,000X) images with minimal beam damage to the frozen-hydrated samples as well as minimal charging effects...
2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27352852/coevolution-of-urat1-and-uricase-during-primate-evolution-implications-for-serum-urate-homeostasis-and-gout
#10
Philip K Tan, Jennifer E Farrar, Eric A Gaucher, Jeffrey N Miner
Uric acid is the highly insoluble end-product of purine metabolism in humans. Serum levels exceeding the solubility threshold can trigger formation of urate crystals resulting in gouty arthritis. Uric acid is primarily excreted through the kidneys with 90% reabsorbed back into the bloodstream through the uric acid transporter URAT1. This reabsorption process is essential for the high serum uric acid levels found in humans. We discovered that URAT1 proteins from humans and baboons have higher affinity for uric acid compared with transporters from rats and mice...
September 2016: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/27291401/ancestral-tryptophan-synthase-reveals-functional-sophistication-of-primordial-enzyme-complexes
#11
Florian Busch, Chitra Rajendran, Kristina Heyn, Sandra Schlee, Rainer Merkl, Reinhard Sterner
Modern enzyme complexes are characterized by a high catalytic efficiency and allosteric communication between the constituting protein subunits. We were interested in whether primordial enzyme complexes from extinct species displayed a similar degree of functional sophistication. To this end, we used ancestral sequence reconstruction to resurrect the α and β subunits of the tryptophan synthase (TS) complex from the last bacterial common ancestor (LBCA), which presumably existed more than 3.4 billion years ago...
June 23, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27253436/selection-for-protein-kinetic-stability-connects-denaturation-temperatures-to-organismal-temperatures-and-provides-clues-to-archaean-life
#12
M Luisa Romero-Romero, Valeria A Risso, Sergio Martinez-Rodriguez, Eric A Gaucher, Beatriz Ibarra-Molero, Jose M Sanchez-Ruiz
The relationship between the denaturation temperatures of proteins (Tm values) and the living temperatures of their host organisms (environmental temperatures: TENV values) is poorly understood. Since different proteins in the same organism may show widely different Tm's, no simple universal relationship between Tm and TENV should hold, other than Tm≥TENV. Yet, when analyzing a set of homologous proteins from different hosts, Tm's are oftentimes found to correlate with TENV's but this correlation is shifted upward on the Tm axis...
2016: PloS One
https://www.readbyqxmd.com/read/27221322/polyphosphate-popping-up-from-oblivion
#13
Javier Jiménez, Samuel Bru, Mariana P C Ribeiro, Josep Clotet
Phosphate is one of the essential elements supporting life. Cells accumulate phosphate in the form of a molecule called polyphosphate (polyP), which carries many functions in the physiology of cells that have not been wholly elucidated. Polyphosphate is present in all the types of cells from bacteria to mammals. It consists of a linear polymer constructed with anywhere from a few to hundreds of inorganic phosphate (Pi) molecules linked by phosphoanhydride bonds. Although polyP was described many years ago, difficulties in the study of its roles, most likely due to the many processes polyP is involved in and incomplete information obtained from multiple models and organisms relegate polyP into oblivion...
May 25, 2016: Current Genetics
https://www.readbyqxmd.com/read/27213181/de-novo-sequencing-and-resurrection-of-a-human-astrovirus-neutralizing-antibody
#14
Walter A Bogdanoff, David Morgenstern, Marshall Bern, Beatrix M Ueberheide, Alicia Sanchez-Fauquier, Rebecca M DuBois
Monoclonal antibody (mAb) therapeutics targeting cancer, autoimmune diseases, inflammatory diseases, and infectious diseases are growing exponentially. Although numerous panels of mAbs targeting infectious disease agents have been developed, their progression into clinically useful mAbs is often hindered by the lack of sequence information and/or loss of hybridoma cells that produce them. Here we combine the power of crystallography and mass spectrometry to determine the amino acid sequence and glycosylation modification of the Fab fragment of a potent human astrovirus-neutralizing mAb...
May 13, 2016: ACS Infectious Diseases
https://www.readbyqxmd.com/read/27092152/organ-specific-proteomic-dissection-of-selaginella-bryopteris-undergoing-dehydration-and-rehydration
#15
Farah Deeba, Ashutosh K Pandey, Vivek Pandey
To explore molecular mechanisms underlying the physiological response of Selaginella bryopteris, a comprehensive proteome analysis was carried out in roots and fronds undergoing dehydration and rehydration. Plants were dehydrated for 7 days followed by 2 and 24 h of rehydration. In roots out of 59 identified spots, 58 protein spots were found to be up-regulated during dehydration stress. The identified proteins were related to signaling, stress and defense, protein and nucleotide metabolism, carbohydrate and energy metabolism, storage and epigenetic control...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27060669/assembly-function-and-evolution-of-cyanobacterial-carboxysomes
#16
REVIEW
Cheryl A Kerfeld, Matthew R Melnicki
All cyanobacteria contain carboxysomes, RuBisCO-encapsulating bacterial microcompartments that function as prokaryotic organelles. The two carboxysome types, alpha and beta, differ fundamentally in components, assembly, and species distribution. Alpha carboxysomes share a highly-conserved gene organization, with evidence of horizontal gene transfer from chemoautotrophic proteobacteria to the picocyanobacteria, and seem to co-assemble shells concomitantly with aggregation of cargo enzymes. In contrast, beta carboxysomes assemble an enzymatic core first, with an encapsulation peptide playing a critical role in formation of the surrounding shell...
June 2016: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/27018861/rapid-evolution-of-antioxidant-defence-in-a-natural-population-of-daphnia-magna
#17
S Oexle, M Jansen, K Pauwels, R Sommaruga, L De Meester, R Stoks
Natural populations can cope with rapid changes in stressors by relying on sets of physiological defence mechanisms. Little is known onto what extent these physiological responses reflect plasticity and/or genetic adaptation, evolve in the same direction and result in an increased defence ability. Using resurrection ecology, we studied how a natural Daphnia magna population adjusted its antioxidant defence to ultraviolet radiation (UVR) during a period with increasing incident UVR reaching the water surface...
July 2016: Journal of Evolutionary Biology
https://www.readbyqxmd.com/read/26992400/new-features-of-desiccation-tolerance-in-the-lichen-photobiont-trebouxia-gelatinosa-are-revealed-by-a-transcriptomic-approach
#18
Fabio Candotto Carniel, Marco Gerdol, Alice Montagner, Elisa Banchi, Gianluca De Moro, Chiara Manfrin, Lucia Muggia, Alberto Pallavicini, Mauro Tretiach
Trebouxia is the most common lichen-forming genus of aero-terrestrial green algae and all its species are desiccation tolerant (DT). The molecular bases of this remarkable adaptation are, however, still largely unknown. We applied a transcriptomic approach to a common member of the genus, T. gelatinosa, to investigate the alteration of gene expression occurring after dehydration and subsequent rehydration in comparison to cells kept constantly hydrated. We sequenced, de novo assembled and annotated the transcriptome of axenically cultured T...
June 2016: Plant Molecular Biology
https://www.readbyqxmd.com/read/26919272/maltase-protein-of-ogataea-hansenula-polymorpha-is-a-counterpart-to-the-resurrected-ancestor-protein-ancmals-of-yeast-maltases-and-isomaltases
#19
Katrin Viigand, Triinu Visnapuu, Karin Mardo, Anneli Aasamets, Tiina Alamäe
Saccharomyces cerevisiae maltases use maltose, maltulose, turanose and maltotriose as substrates, isomaltases use isomaltose, α-methylglucoside and palatinose and both use sucrose. These enzymes are hypothesized to have evolved from a promiscuous α-glucosidase ancMALS through duplication and mutation of the genes. We studied substrate specificity of the maltase protein MAL1 from an earlier diverged yeast, Ogataea polymorpha (Op), in the light of this hypothesis. MAL1 has extended substrate specificity and its properties are strikingly similar to those of resurrected ancMALS...
August 2016: Yeast
https://www.readbyqxmd.com/read/26858600/bicarbonate-and-ca-2-sensing-modulators-activate-photoreceptor-ros-gc1-synergistically
#20
Teresa Duda, Alexandre Pertzev, Clint L Makino, Rameshwar K Sharma
Photoreceptor ROS-GC1, a prototype subfamily member of the membrane guanylate cyclase family, is a central component of phototransduction. It is a single transmembrane-spanning protein, composed of modular blocks. In rods, guanylate cyclase activating proteins (GCAPs) 1 and 2 bind to its juxtamembrane domain (JMD) and the C-terminal extension, respectively, to accelerate cyclic GMP synthesis when Ca(2+) levels are low. In cones, the additional expression of the Ca(2+)-dependent guanylate cyclase activating protein (CD-GCAP) S100B which binds to its C-terminal extension, supports acceleration of cyclic GMP synthesis at high Ca(2+) levels...
2016: Frontiers in Molecular Neuroscience
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