Hemoglobin

2018 ◽  
Author(s):  
Jay F. Storz
Keyword(s):  
Molecular Evolution ◽  
Structure Function ◽  
Protein Function ◽  
Evolutionary Genetics ◽  
Functional Evolution ◽  
Biochemical Adaptation ◽  
Wide Range ◽  
Single Well ◽  
Sequence Reconstruction ◽  
Evolution Of Proteins

The aims of this book are to provide a synthesis of our current understanding of hemoglobin structure, function, and evolution, and to illustrate how research on this paradigmatic protein has provided general insights into mechanisms of molecular evolution and biochemical adaptation. The book promotes an appreciation of how mechanistic insights into protein function can enrich our understanding of how evolution works and, reciprocally, it highlights how approaches in evolutionary genetics (such as phylogenetic comparative methods and ancestral sequence reconstruction) can be brought to bear on questions about the functional evolution of proteins. This treatise on the functional evolution of hemoglobin illustrates how research on a single, well-chosen model system can enhance our investigative acuity and bring key conceptual questions into sharp focus. Hemoglobin: Insights into Protein Structure, Function, and Evolution is suitable for a wide range of graduate level students taking interdisciplinary courses in biochemical physiology and protein evolution, and will serve as a key reference for researchers in molecular evolution, biochemistry, and comparative physiology.

scholarly journals The role of mutation bias in adaptive molecular evolution: insights from convergent changes in protein function

2019 ◽  
Vol 374 (1777) ◽  
pp. 20180238 ◽  
Author(s):  
Jay F. Storz ◽  
Chandrasekhar Natarajan ◽  
Anthony V. Signore ◽  
Christopher C. Witt ◽  
David M. McCandlish ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Protein Function ◽  
Methylation Status ◽  
Point Mutations ◽  
Evolutionary Genetics ◽  
Mutational Bias ◽  
Missense Mutations ◽  
Mutation Bias ◽  
Cpg Dinucleotides ◽  
Adaptive Molecular Evolution

An underexplored question in evolutionary genetics concerns the extent to which mutational bias in the production of genetic variation influences outcomes and pathways of adaptive molecular evolution. In the genomes of at least some vertebrate taxa, an important form of mutation bias involves changes at CpG dinucleotides: if the DNA nucleotide cytosine (C) is immediately 5′ to guanine (G) on the same coding strand, then—depending on methylation status—point mutations at both sites occur at an elevated rate relative to mutations at non-CpG sites. Here, we examine experimental data from case studies in which it has been possible to identify the causative substitutions that are responsible for adaptive changes in the functional properties of vertebrate haemoglobin (Hb). Specifically, we examine the molecular basis of convergent increases in Hb–O 2 affinity in high-altitude birds. Using a dataset of experimentally verified, affinity-enhancing mutations in the Hbs of highland avian taxa, we tested whether causative changes are enriched for mutations at CpG dinucleotides relative to the frequency of CpG mutations among all possible missense mutations. The tests revealed that a disproportionate number of causative amino acid replacements were attributable to CpG mutations, suggesting that mutation bias can influence outcomes of molecular adaptation. This article is part of the theme issue ‘Convergent evolution in the genomics era: new insights and directions’.

scholarly journals Growth Promotion or Osmotic Stress Response: How SNF1-Related Protein Kinase 2 (SnRK2) Kinases Are Activated and Manage Intracellular Signaling in Plants

Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1443
Author(s):  
Yoshiaki Kamiyama ◽  
Sotaro Katagiri ◽  
Taishi Umezawa
Keyword(s):  
Protein Kinase ◽  
Plant Growth ◽  
Osmotic Stress ◽  
Protein Function ◽  
Intracellular Signaling ◽  
Growth Promotion ◽  
Research Field ◽  
Dependent Manner ◽  
Related Protein ◽  
Wide Range

Reversible phosphorylation is a major mechanism for regulating protein function and controls a wide range of cellular functions including responses to external stimuli. The plant-specific SNF1-related protein kinase 2s (SnRK2s) function as central regulators of plant growth and development, as well as tolerance to multiple abiotic stresses. Although the activity of SnRK2s is tightly regulated in a phytohormone abscisic acid (ABA)-dependent manner, recent investigations have revealed that SnRK2s can be activated by group B Raf-like protein kinases independently of ABA. Furthermore, evidence is accumulating that SnRK2s modulate plant growth through regulation of target of rapamycin (TOR) signaling. Here, we summarize recent advances in knowledge of how SnRK2s mediate plant growth and osmotic stress signaling and discuss future challenges in this research field.

scholarly journals Molecular evolution of proteins on filamentous phage. Mimicking the strategy of the immune system.

1992 ◽  
Vol 267 (23) ◽  
pp. 16007-16010
Author(s):  
J.D. Marks ◽  
H.R. Hoogenboom ◽  
A.D. Griffiths ◽  
G Winter
Keyword(s):  
Immune System ◽  
Molecular Evolution ◽  
Filamentous Phage ◽  
Evolution Of Proteins

scholarly journals Rapid and Programmable Protein Mutagenesis Using Plasmid Recombineering

2017 ◽  
Author(s):  
Sean A. Higgins ◽  
Sorel Ouonkap ◽  
David F. Savage
Keyword(s):  
Structure Function ◽  
Sequence Space ◽  
Protein Function ◽  
Fluorescent Protein ◽  
One Pot ◽  
Protein Mutagenesis ◽  
Protein Mutants ◽  
Protein Libraries

ABSTRACTComprehensive and programmable protein mutagenesis is critical for understanding structure-function relationships and improving protein function. However, current techniques enabling comprehensive protein mutagenesis are based on PCR and require in vitro reactions involving specialized protocols and reagents. This has complicated efforts to rapidly and reliably produce desired comprehensive protein libraries. Here we demonstrate that plasmid recombineering is a simple and robust in vivo method for the generation of protein mutants for both comprehensive library generation as well as programmable targeting of sequence space. Using the fluorescent protein iLOV as a model target, we build a complete mutagenesis library and find it to be specific and unbiased, detecting 99.8% of our intended mutations. We then develop a thermostability screen and utilize our comprehensive mutation data to rapidly construct a targeted and multiplexed library that identifies significantly improved variants, thus demonstrating rapid protein engineering in a simple one-pot protocol.

scholarly journals Inference of distribution of fitness effects and proportion of adaptive substitutions from polymorphism data

2016 ◽  
Author(s):  
Paula Tataru ◽  
Maéva Mollion ◽  
Sylvain Glemin ◽  
Thomas Bataillon
Keyword(s):  
Molecular Evolution ◽  
Evolutionary Genetics ◽  
Deleterious Mutations ◽  
Probabilistic Framework ◽  
Evolutionary Trajectory ◽  
Beneficial Mutations ◽  
Fitness Effects ◽  
Polymorphism Data ◽  
Inference Methods ◽  
Biased Estimates

ABSTRACTThe distribution of fitness effects (DFE) encompasses deleterious, neutral and beneficial mutations. It conditions the evolutionary trajectory of populations, as well as the rate of adaptive molecular evolution (α). Inference of DFE and α from patterns of polymorphism (SFS) and divergence data has been a longstanding goal of evolutionary genetics. A widespread assumption shared by numerous methods developed so far to infer DFE and α from such data is that beneficial mutations contribute only negligibly to the polymorphism data. Hence, a DFE comprising only deleterious mutations tends to be estimated from SFS data, and α is only predicted by contrasting the SFS with divergence data from an outgroup. Here, we develop a hierarchical probabilistic framework that extends on previous methods and also can infer DFE and α from polymorphism data alone. We use extensive simulations to examine the performance of our method. We show that both a full DFE, comprising both deleterious and beneficial mutations, and α can be inferred without resorting to divergence data. We demonstrate that inference of DFE from polymorphism data alone can in fact provide more reliable estimates, as it does not rely on strong assumptions about a shared DFE between the outgroup and ingroup species used to obtain the SFS and divergence data. We also show that not accounting for the contribution of beneficial mutations to polymorphism data leads to substantially biased estimates of the DFE and α. We illustrate these points using our newly developed framework, while also comparing to one of the most widely used inference methods available.

scholarly journals When Coupled to Natural Transformation in Acinetobacter sp. Strain ADP1, PCR Mutagenesis Is Made Less Random by Mismatch Repair

2005 ◽  
Vol 71 (11) ◽  
pp. 7610-7612 ◽  
Author(s):  
Alison Buchan ◽  
L. Nicholas Ornston
Keyword(s):  
Structure Function ◽  
Mismatch Repair ◽  
Protein Function ◽  
Natural Transformation ◽  
Function Analysis ◽  
Repair System ◽  
Loss Of Function ◽  
Nucleotide Substitutions ◽  
Full Spectrum ◽  
Mismatch Repair System

ABSTRACT Random PCR mutagenesis is a powerful tool for structure-function analysis of targeted proteins, especially when coupled with DNA integration through natural transformation followed by selection for loss of function. The technique has been applied successfully to structure-function analysis of transcriptional regulators, enzymes, and transporters in Acinetobacter sp. strain ADP1. However, the mismatch repair system prevents the full spectrum of nucleotide substitutions that may be selected at the level of protein function from being recovered. This barrier may be overcome by introducing PCR-mutagenized genes into strains in which the corresponding genes have been deleted.

LARMD: integration of bioinformatic resources to profile ligand-driven protein dynamics with a case on the activation of estrogen receptor

2019 ◽  
Vol 21 (6) ◽  
pp. 2206-2218 ◽  
Author(s):  
Jing-Fang Yang ◽  
Fan Wang ◽  
Yu-Zong Chen ◽  
Ge-Fei Hao ◽  
Guang-Fu Yang
Keyword(s):  
Estrogen Receptor ◽  
Protein Dynamics ◽  
Protein Function ◽  
Inflammatory Diseases ◽  
Great Difficulty ◽  
Vital Role ◽  
Site Directed Mutagenesis ◽  
Bioinformatic Tools ◽  
Wide Range ◽  
User Friendly

Abstract Protein dynamics is central to all biological processes, including signal transduction, cellular regulation and biological catalysis. Among them, in-depth exploration of ligand-driven protein dynamics contributes to an optimal understanding of protein function, which is particularly relevant to drug discovery. Hence, a wide range of computational tools have been designed to investigate the important dynamic information in proteins. However, performing and analyzing protein dynamics is still challenging due to the complicated operation steps, giving rise to great difficulty, especially for nonexperts. Moreover, there is a lack of web protocol to provide online facility to investigate and visualize ligand-driven protein dynamics. To this end, in this study, we integrated several bioinformatic tools to develop a protocol, named Ligand and Receptor Molecular Dynamics (LARMD, http://chemyang.ccnu.edu.cn/ccb/server/LARMD/ and http://agroda.gzu.edu.cn:9999/ccb/server/LARMD/), for profiling ligand-driven protein dynamics. To be specific, estrogen receptor (ER) was used as a case to reveal ERβ-selective mechanism, which plays a vital role in the treatment of inflammatory diseases and many types of cancers in clinical practice. Two different residues (Ile373/Met421 and Met336/Leu384) in the pocket of ERβ/ERα were the significant determinants for selectivity, especially Met336 of ERβ. The helix H8, helix H11 and H7-H8 loop influenced the migration of selective agonist (WAY-244). These computational results were consistent with the experimental results. Therefore, LARMD provides a user-friendly online protocol to study the dynamic property of protein and to design new ligand or site-directed mutagenesis.

scholarly journals Yeast Chemogenetic Screening as a Tool to Unravel the Antifungal Mode of Action of Two Selected Selenocyanates

2019 ◽  
Vol 9 (18) ◽  
pp. 3728 ◽  
Author(s):  
Sarfraz ◽  
Nasim ◽  
Jacob ◽  
Gruhlke
Keyword(s):  
Anticancer Agents ◽  
Protein Function ◽  
Mode Of Action ◽  
Biological Activities ◽  
Resistance Mechanisms ◽  
Yeast Cells ◽  
Cytotoxic Activities ◽  
Organoselenium Compounds ◽  
Arabidopsis Mutants ◽  
Wide Range

During recent decades, selenium-containing compounds, as with the chemically similar sulfur-containing compounds, have gained considerable interest as cytotoxic and anticancer agents. Selenocyanates represent a well-established class of organic selenium compounds. These agents exhibit a wide range of biological activities. Classically, selenocyanates may cause an increase in the intracellular levels of reactive oxygen species (ROS) and exert cytotoxic activities, thus, acting as pro-oxidants. In this study, chemogenetic profiling was carried out to decipher the resistance mechanisms as central part of the antifungal mode of action against two selected selenocyanates. If a mutant line is less resistant against a compound compared to the wildtype, the gene deleted in that strain seems to be correlated with the resistance. Yeast mutants carrying gene deletions for specific redox-related protein function were employed in the chemogenetic screening. The results of screening reveal the hypersensitivity of mutants carrying deletions for glutathione pool and metabolism. To confirm the results, Arabidopsis mutants deficient in glutathione were subjected to various concentrations of selenocyanates to observe their effects on mutants and the wildtype. A significant dose dependent inhibition in Arabidopsis mutants compared to the wildtype confirmed the findings of the chemogenetic screening. The data suggest that the two representatives of organoselenium compounds cause oxidative stress in yeast cells and glutathione participates towards the development of resistance against the chemicals.

scholarly journals Laboratory-Directed Protein Evolution

2005 ◽  
Vol 69 (3) ◽  
pp. 373-392 ◽  
Author(s):  
Ling Yuan ◽  
Itzhak Kurek ◽  
James English ◽  
Robert Keenan
Keyword(s):  
Protein Evolution ◽  
Selective Pressure ◽  
Evolutionary Potential ◽  
Effective Strategies ◽  
Scientific Disciplines ◽  
Wide Range ◽  
Protein Functions ◽  
Evolution Of Proteins ◽  
Efficient Screening ◽  
New Protein

SUMMARY Systematic approaches to directed evolution of proteins have been documented since the 1970s. The ability to recruit new protein functions arises from the considerable substrate ambiguity of many proteins. The substrate ambiguity of a protein can be interpreted as the evolutionary potential that allows a protein to acquire new specificities through mutation or to regain function via mutations that differ from the original protein sequence. All organisms have evolutionarily exploited this substrate ambiguity. When exploited in a laboratory under controlled mutagenesis and selection, it enables a protein to “evolve” in desired directions. One of the most effective strategies in directed protein evolution is to gradually accumulate mutations, either sequentially or by recombination, while applying selective pressure. This is typically achieved by the generation of libraries of mutants followed by efficient screening of these libraries for targeted functions and subsequent repetition of the process using improved mutants from the previous screening. Here we review some of the successful strategies in creating protein diversity and the more recent progress in directed protein evolution in a wide range of scientific disciplines and its impacts in chemical, pharmaceutical, and agricultural sciences.

Functional Evolution of Proteins

2007 ◽  
Vol 2007 (404) ◽  
pp. tw340-tw340
Author(s):  
V. J. Vinson
Keyword(s):  
Functional Evolution ◽  
Evolution Of Proteins
Sign in / Sign up

Export Citation Format

Share Document