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Protein resurrection

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https://www.readbyqxmd.com/read/29188989/identification-and-experimental-characterization-of-an-extremophilic-brine-pool-alcohol-dehydrogenase-from-single-amplified-genomes
#1
Stefan W Grötzinger, Ram Karan, Eva Strillinger, Stefan Bader, Annika Frank, Israa S Al Rowaihi, Anastassja Akal, Wiebke Wackerow, John A Archer, Magnus Rueping, Dirk Weuster-Botz, Michael Groll, Jörg Eppinger, Stefan T Arold
Because only 0.01% of prokaryotic genospecies can be cultured and in situ observations are often impracticable, culture-independent methods are required to understand microbial life and harness potential applications of microbes. Here, we report a methodology for the production of proteins with desired functions based on single amplified genomes (SAGs) from unculturable species. We use this method to resurrect an alcohol dehydrogenase (ADH/D1) from an uncharacterized halo-thermophilic archaeon collected from a brine pool at the bottom of the Red Sea...
November 30, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29150287/anastasis-and-the-er-stress-response-solving-the-paradox-of-the-unfolded-protein-response-in-cancer
#2
Rafael Vincent M Manalo
In recent years, studies have suggested a novel pathway for cell survival, which faces scientific skepticism and interest in its concept of cell 'resurrection' - that is, the anastasis of cells at late-stage apoptosis. While biomarkers have been discovered, many of these are related to the endoplasmic reticulum (ER) stress response - acting also to promote cell survival in the presence of perturbation. The promises of anastasis, if accepted, will greatly impact translational medicine especially in the treatment of cancer, since apoptosis is generally irreversible in the late stages, and chemotherapy is performed to maximize tumor death and minimize off-target effects...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29142064/the-resurrection-of-the-piddosome-emerging-roles-in-the-dna-damage-response-and-centrosome-surveillance
#3
REVIEW
Valentina Sladky, Fabian Schuler, Luca L Fava, Andreas Villunger
The PIDDosome is often used as the alias for a multi-protein complex that includes the p53-induced death domain protein 1 (PIDD1), the bipartite linker protein CRADD (also known as RAIDD) and the pro-form of an endopeptidase belonging to the caspase family, i.e. caspase-2. Yet, PIDD1 variants can also interact with a number of other proteins that include RIPK1 (also known as RIP1) and IKBKG (also known as NEMO), PCNA and RFC5, as well as nucleolar components such as NPM1 or NCL. This promiscuity in protein binding is facilitated mainly by autoprocessing of the full-length protein into various fragments that contain different structural domains...
November 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29133450/resurrecting-ancestral-genes-in-bacteria-to-interpret-ancient-biosignatures
#4
Betul Kacar, Lionel Guy, Eric Smith, John Baross
Two datasets, the geologic record and the genetic content of extant organisms, provide complementary insights into the history of how key molecular components have shaped or driven global environmental and macroevolutionary trends. Changes in global physico-chemical modes over time are thought to be a consistent feature of this relationship between Earth and life, as life is thought to have been optimizing protein functions for the entirety of its approximately 3.8 billion years of history on the Earth. Organismal survival depends on how well critical genetic and metabolic components can adapt to their environments, reflecting an ability to optimize efficiently to changing conditions...
December 28, 2017: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
https://www.readbyqxmd.com/read/29036694/efficient-modulation-of-photosynthetic-apparatus-confers-desiccation-tolerance-in-the-resurrection-plant-boea-hygrometrica
#5
Tinghong Tan, Yanni Sun, Shishuai Luo, Chao Zhang, Huapeng Zhou, Honghui Lin
Boea hygrometrica (B. hygrometrica) can tolerate severe desiccation and resume photosynthetic activity rapidly upon water availability. However, little is known about the mechanisms by which B. hygrometrica adapts to dehydration and resumes competence upon rehydration. Here we determine how B. hygrometrica deals with oxidative stress, excessive excitation/electron pressures as well as photosynthetic apparatus modulation during dehydration/rehydration. By measuring ROS generation and scavenging efficiency, we found that B...
November 1, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28916155/ancestral-resurrection-of-anthropoid-estrogen-receptor-%C3%AE-demonstrates-functional-consequences-of-positive-selection
#6
Amy Weckle, Michael R McGowen, Jun Xing, Caoyi Chen, Kirstin N Sterner, Zhuo-Cheng Hou, Roberto Romero, Derek E Wildman
Anthropoid primates arose during the Eocene approximately 55 million years ago (mya), and extant anthropoids share a most recent common ancestor ∼40mya. Paleontology has been very successful at describing the morphological phenotypes of extinct anthropoids. Less well understood is the molecular biology of these extinct species as well as the phenotypic consequences of evolutionary variation in their genomes. Here we resurrect the most recent common ancestral anthropoid estrogen receptor β gene (ESR2) and demonstrate that the function of this ancestral estrogen receptor has been maintained during human descent but was altered during early New World monkey (NWM) evolution by becoming a more potent transcriptional activator...
September 13, 2017: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/28851849/functional-constraints-on-replacing-an-essential-gene-with-its-ancient-and-modern-homologs
#7
Betül Kacar, Eva Garmendia, Nurcan Tuncbag, Dan I Andersson, Diarmaid Hughes
Genes encoding proteins that carry out essential informational tasks in the cell, in particular where multiple interaction partners are involved, are less likely to be transferable to a foreign organism. Here, we investigated the constraints on transfer of a gene encoding a highly conserved informational protein, translation elongation factor Tu (EF-Tu), by systematically replacing the endogenous tufA gene in the Escherichia coli genome with its extant and ancestral homologs. The extant homologs represented tuf variants from both near and distant homologous organisms...
August 29, 2017: MBio
https://www.readbyqxmd.com/read/28840559/personalized-medicine-and-resurrected-hopes-for-the-management-of-alzheimer-s-disease-a-modular-approach-based-on-gsk-3%C3%AE-inhibitors
#8
Reem K Arafa, Nehal H Elghazawy
Alzheimer's disease (AD) is one of the most common neurological disorders with vast reaching worldwide prevalence. Research attempts to decipher what's happening to the human mind have shown that pathogenesis of AD is associated with misfolded protein intermediates displaying tertiary structure conformational changes eventually leading to forming large polymers of unwanted aggregates. The two hallmarks of AD pathological protein aggregates are extraneuronal β-amyloid (Aβ) based senile plaques and intraneuronal neurofibrillary tangles (NFTs)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28726643/reconstructed-ancestral-enzymes-reveal-that-negative-selection-drove-the-evolution-of-substrate-specificity-in-adp-dependent-kinases
#9
Víctor Castro-Fernandez, Alejandra Herrera-Morande, Ricardo Zamora, Felipe Merino, Felipe Gonzalez-Ordenes, Felipe Padilla-Salinas, Humberto M Pereira, Jose Brandão-Neto, Richard C Garratt, Victoria Guixe
One central goal in molecular evolution is to pinpoint the mechanisms and evolutionary forces that cause an enzyme to change its substrate specificity; however, these processes remain largely unexplored. Using the glycolytic ADP-dependent kinases of archaea, including the orders Thermococcales, Methanosarcinales, and Methanococcales, as a model and employing an approach involving paleoenzymology, evolutionary statistics, and protein structural analysis, we could track changes in substrate specificity during ADP-dependent kinase evolution along with the structural determinants of these changes...
September 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28719578/de-novo-active-sites-for-resurrected-precambrian-enzymes
#10
Valeria A Risso, Sergio Martinez-Rodriguez, Adela M Candel, Dennis M Krüger, David Pantoja-Uceda, Mariano Ortega-Muñoz, Francisco Santoyo-Gonzalez, Eric A Gaucher, Shina C L Kamerlin, Marta Bruix, Jose A Gavira, Jose M Sanchez-Ruiz
Protein engineering studies often suggest the emergence of completely new enzyme functionalities to be highly improbable. However, enzymes likely catalysed many different reactions already in the last universal common ancestor. Mechanisms for the emergence of completely new active sites must therefore either plausibly exist or at least have existed at the primordial protein stage. Here, we use resurrected Precambrian proteins as scaffolds for protein engineering and demonstrate that a new active site can be generated through a single hydrophobic-to-ionizable amino acid replacement that generates a partially buried group with perturbed physico-chemical properties...
July 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28689969/ancestral-reconstruction-approach-to-acetylcholine-receptor-structure-and-function
#11
Jethro E Prinston, Johnathon R Emlaw, Mathieu F Dextraze, Christian J G Tessier, F Javier Pérez-Areales, Melissa S McNulty, Corrie J B daCosta
Acetylcholine receptors (AChRs) are members of a superfamily of proteins called pentameric ligand-gated ion channels, which are found in almost all forms of life and thus have a rich evolutionary history. Muscle-type AChRs are heteropentameric complexes assembled from four related subunits (α, β, δ, and ɛ). Here we reconstruct the amino acid sequence of a β subunit ancestor shared by humans and cartilaginous fishes (i.e., Torpedo). Then, by resurrecting this ancestral β subunit and co-expressing it with human α, δ, and ɛ subunits, we show that despite 132 substitutions, the ancestral subunit is capable of forming human/ancestral hybrid AChRs...
August 1, 2017: Structure
https://www.readbyqxmd.com/read/28671667/mechanochemical-evolution-of-the-giant-muscle-protein-titin-as-inferred-from-resurrected-proteins
#12
Aitor Manteca, Jörg Schönfelder, Alvaro Alonso-Caballero, Marie J Fertin, Nerea Barruetabeña, Bruna F Faria, Elias Herrero-Galán, Jorge Alegre-Cebollada, David De Sancho, Raul Perez-Jimenez
The sarcomere-based structure of muscles is conserved among vertebrates; however, vertebrate muscle physiology is extremely diverse. A molecular explanation for this diversity and its evolution has not been proposed. We use phylogenetic analyses and single-molecule force spectroscopy (smFS) to investigate the mechanochemical evolution of titin, a giant protein responsible for the elasticity of muscle filaments. We resurrect eight-domain fragments of titin corresponding to the common ancestors to mammals, sauropsids, and tetrapods, which lived 105-356 Myr ago, and compare them with titin fragments from some of their modern descendants...
August 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28652896/resurrecting-the-dead-molecules
#13
REVIEW
Jan Zaucha, Jonathan G Heddle
Biological molecules, like organisms themselves, are subject to genetic drift and may even become "extinct". Molecules that are no longer extant in living systems are of high interest for several reasons including insight into how existing life forms evolved and the possibility that they may have new and useful properties no longer available in currently functioning molecules. Predicting the sequence/structure of such molecules and synthesizing them so that their properties can be tested is the basis of "molecular resurrection" and may lead not only to a deeper understanding of evolution, but also to the production of artificial proteins with novel properties and even to insight into how life itself began...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/28627478/a-glimpse-into-the-specialization-history-of-the-lipases-acyltransferases-family-of-cplip2
#14
COMPARATIVE STUDY
Anne-Hélène Jan, Eric Dubreucq, Jullien Drone, Maeva Subileau
Lipases/acyltransferases homologous to CpLIP2 from Candida parapsilosis belong to the α/β hydrolase superfamily as lipase A from Moesziomyces antarcticus (Candida antarctica), and constitute a consistent phylogenetic subgroup with at least 56% identity. Lipases/acyltransferases share the phenotypic characteristic of a high acyltransfer activity even in aqueous media with very high water thermodynamic activity. Previous mutagenesis and evolution strategies have given insights into the role of key residues and protein subdomains in the reaction and substrate specificities of these enzymes...
September 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28622918/angiosperm-plant-desiccation-tolerance-hints-from-transcriptomics-and-genome-sequencing
#15
REVIEW
Valentino Giarola, Quancan Hou, Dorothea Bartels
Desiccation tolerance (DT) in angiosperms is present in the small group of resurrection plants and in seeds. DT requires the presence of protective proteins, specific carbohydrates, restructuring of membrane lipids, and regulatory mechanisms directing a dedicated gene expression program. Many components are common to resurrection plants and seeds; however, some are specific for resurrection plants. Understanding how each component contributes to DT is challenging. Recent transcriptome analyses and genome sequencing indicate that increased expression is essential of genes encoding protective components, recently evolved, species-specific genes and non-protein-coding RNAs...
August 2017: Trends in Plant Science
https://www.readbyqxmd.com/read/28578406/ancestral-protein-resurrection-and-engineering-opportunities-of-the-mamba-aminergic-toxins
#16
Guillaume Blanchet, Doria Alili, Adèle Protte, Gregory Upert, Nicolas Gilles, Livia Tepshi, Enrico A Stura, Gilles Mourier, Denis Servent
Mamba venoms contain a multiplicity of three-finger fold aminergic toxins known to interact with various α-adrenergic, muscarinic and dopaminergic receptors with different pharmacological profiles. In order to generate novel functions on this structural scaffold and to avoid the daunting task of producing and screening an overwhelming number of variants generated by a classical protein engineering strategy, we accepted the challenge of resurrecting ancestral proteins, likely to have possessed functional properties...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28494872/using-resurrected-ancestral-proviral-proteins-to-engineer-virus-resistance
#17
Asunción Delgado, Rocio Arco, Beatriz Ibarra-Molero, Jose M Sanchez-Ruiz
Proviral factors are host proteins hijacked by viruses for processes essential for virus propagation such as cellular entry and replication. Pathogens and their hosts co-evolve. It follows that replacing a proviral factor with a functional ancestral form of the same protein could prevent viral propagation without fatally compromising organismal fitness. Here, we provide proof of concept of this notion. Thioredoxins serve as general oxidoreductases in all known cells. We report that several laboratory resurrections of Precambrian thioredoxins display substantial levels of functionality within Escherichia coli...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28466470/an-osmotin-from-the-resurrection-plant-tripogon-loliiformis-tlosm-confers-tolerance-to-multiple-abiotic-stresses-in-transgenic-rice
#18
Thi Thuy Trang Le, Brett Williams, Sagadevan Mundree
Osmotin is a key protein associated with abiotic and biotic stress response in plants. In this study, an osmotin from the resurrection plant Tripogon loliiformis (TlOsm) was characterized and functionally analyzed under abiotic stress conditions in T. loliiformis as well as in transgenic Nicotiana tabacum (tobacco) and Oryza sativa (rice) plants. Real-time PCR analysis on mixed elicitor cDNA libraries from T. loliiformis showed that TlOsm was upregulated a thousand-fold during the early stages of osmotic stresses (cold, drought, and salinity) in both shoots and roots but down-regulated in shoots during heat stress...
May 3, 2017: Physiologia Plantarum
https://www.readbyqxmd.com/read/28419658/ancestral-haloalkane-dehalogenases-show-robustness-and-unique-substrate-specificity
#19
Petra Babkova, Eva Sebestova, Jan Brezovsky, Radka Chaloupkova, Jiri Damborsky
Ancestral sequence reconstruction (ASR) represents a powerful approach for empirical testing structure-function relationships of diverse proteins. We employed ASR to predict sequences of five ancestral haloalkane dehalogenases (HLDs) from the HLD-II subfamily. Genes encoding the inferred ancestral sequences were synthesized and expressed in Escherichia coli, and the resurrected ancestral enzymes (AncHLD1-5) were experimentally characterized. Strikingly, the ancestral HLDs exhibited significantly enhanced thermodynamic stability compared to extant enzymes (ΔTm up to 24 °C), as well as higher specific activities with preference for short multi-substituted halogenated substrates...
July 18, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28398197/emergence-and-evolution-of-an-interaction-between-intrinsically-disordered-proteins
#20
Greta Hultqvist, Emma Åberg, Carlo Camilloni, Gustav N Sundell, Eva Andersson, Jakob Dogan, Celestine N Chi, Michele Vendruscolo, Per Jemth
Protein-protein interactions involving intrinsically disordered proteins are important for cellular function and common in all organisms. However, it is not clear how such interactions emerge and evolve on a molecular level. We performed phylogenetic reconstruction, resurrection and biophysical characterization of two interacting disordered protein domains, CID and NCBD. CID appeared after the divergence of protostomes and deuterostomes 450-600 million years ago, while NCBD was present in the protostome/deuterostome ancestor...
April 11, 2017: ELife
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