Explanipedia

Systematic profiling of dominant ubiquitin variants reveals key functional nodes contributing to evolutionary selection Open

Amrita Arpita Padhy, David Mavor, Subhashree Sahoo, Daniel N. Bolon, Parul Mishra · 2023

Dominant-negative mutations can help to investigate the biological mechanisms and to understand the selective pressures for multifunctional proteins. However, most studies have focused on recessive mutant effects that occur in the absence …

A complete allosteric map of a GTPase switch in its native cellular network Open

Christopher J.P. Mathy, Parul Mishra, Julia M. Flynn, Tina Perica, David Mavor , et al. · 2023

Allosteric regulation is central to protein function in cellular networks. A fundamental open question is whether cellular regulation of allosteric proteins occurs only at a few defined positions or at many sites distributed throughout the…

A complete allosteric map of a GTPase switch in its native network Open

Christopher J.P. Mathy, Parul Mishra, Julia M. Flynn, Tina Perica, David Mavor , et al. · 2022

Allosteric regulation is central to protein function in cellular networks 1 . However, despite technological advances 2,3 most studies of allosteric effects on function are conducted in heterologous environments 2,4,5 , limiting the discov…

Analyses of HIV proteases variants at the threshold of viability reveals relationships between processing efficiency and fitness Open

Gily Schneider-Nachum, Julia M. Flynn, David Mavor, Celia A. Schiffer, Daniel N. Bolon · 2021

Investigating the relationships between protein function and fitness provides keys for understanding biochemical mechanisms that underly evolution. Mutations with partial fitness defects can delineate the threshold of biochemical function …

Genetic interaction mapping informs integrative structure determination of protein complexes Open

Hannes Braberg, Ignacia Echeverria, Stefan Bohn, Peter Cimermančič, Anthony L. Shiver , et al. · 2020

From phenotype to structure Much insight has come from structures of macromolecular complexes determined by methods such as crystallography or cryo–electron microscopy. However, looking at transient complexes remains challenging, as does d…

The Adaptive Potential of the Middle Domain of Yeast Hsp90 Open

Pamela A. Cote-Hammarlof, Inês Fragata, Julia M. Flynn, David Mavor, Konstantin B. Zeldovich , et al. · 2020

The distribution of fitness effects (DFEs) of new mutations across different environments quantifies the potential for adaptation in a given environment and its cost in others. So far, results regarding the cost of adaptation across enviro…

Comprehensive fitness maps of Hsp90 show widespread environmental dependence Open

Julia M. Flynn, Ammeret Rossouw, Pamela A. Cote-Hammarlof, Inês Fragata, David Mavor , et al. · 2020

Gene-environment interactions have long been theorized to influence molecular evolution. However, the environmental dependence of most mutations remains unknown. Using deep mutational scanning, we engineered yeast with all 44,604 single co…

Author response: Comprehensive fitness maps of Hsp90 show widespread environmental dependence Open

Julia M. Flynn, Ammeret Rossouw, Pamela A. Cote-Hammarlof, Inês Fragata, David Mavor , et al. · 2020

Investigating the influence of environment on the evolution of Hsp90 using comprehensive fitness maps [preprint] Open

Julia M. Flynn, Ammeret Rossouw, Pamela A. Cote-Hammarlof, Inês Fragata, David Mavor , et al. · 2019

Gene-environment interactions have long been theorized to influence molecular evolution. However, the environmental dependence of most mutations remains unknown. Using deep mutational scanning, we engineered budding yeast with all 44,604 s…

Mapping the growth effect of previously hidden ubiquitin alleles using an overexpression based mutational scan Open

David Mavor, Daniel N. Bolon, Parul Mishra · 2019

Deep mutational scanning has emerged as a powerful, high throughput approach to determine the growth effect of thousands of alleles at once in bulk competition. However, to date only the growth effect of mutant alleles in isolation has bee…

The adaptive potential of the middle domain of yeast Hsp90 Open

Pamela A. Cote-Hammarlof, Inês Fragata, Julia M. Flynn, David Mavor, Konstantin B. Zeldovich , et al. · 2019

The distribution of fitness effects (DFE) of new mutations across different environments quantifies the potential for adaptation in a given environment and its cost in others. So far, results regarding the cost of adaptation across environ…

Comprehensive fitness maps of Hsp90 show widespread environmental dependence Open

Julia M. Flynn, Ammeret Rossouw, Pamela A. Cote-Hammarlof, Inês Fragata, David Mavor , et al. · 2019

Gene-environment interactions have long been theorized to influence molecular evolution. However, the environmental dependence of most mutations remains unknown. Using deep mutational scanning, we engineered yeast with all 44,604 single co…

Extending chemical perturbations of the ubiquitin fitness landscape in a classroom setting reveals new constraints on sequence tolerance Open

David Mavor, Kyle A. Barlow, Daniel Asarnow, Yuliya Birman, Derek Britain , et al. · 2018

Although the primary protein sequence of ubiquitin (Ub) is extremely stable over evolutionary time, it is highly tolerant to mutation during selection experiments performed in the laboratory. We have proposed that this discrepancy results …

Rescue of conformational dynamics in enzyme catalysis by directed evolution Open

Renee Otten, Lin Liu, Lukas Kenner, Michael W. Clarkson, David Mavor , et al. · 2018

Rescue of Conformational Dynamics in Enzyme Catalysis by Directed Evolution Open

Renee Otten, Lin Liu, Lillian R. Kenner, Michael W. Clarkson, David Mavor , et al. · 2017

Rational design and directed evolution have proved to be successful approaches to increase catalytic efficiencies of both natural and artificial enzymes 1-3 . However, a comprehensive understanding of how evolution shapes the energy landsc…

Determination of the Ubiquitin Fitness Landscape Under Seventeen Chemical Conditions in a Classroom Setting Open

David Mavor · 2017

Ubiquitin is essential for eukaryotic life and varies in only 3 amino acid positions between yeast and humans. However, recent deep sequencing studies indicate that ubiquitin is highly tolerant to single mutations. We hypothesized that thi…

Determination of ubiquitin fitness landscapes under different chemical stresses in a classroom setting Open

David Mavor, Kyle A. Barlow, Samuel Thompson, Benjamin A. Barad, Alain R. Bonny , et al. · 2016

Ubiquitin is essential for eukaryotic life and varies in only 3 amino acid positions between yeast and humans. However, recent deep sequencing studies indicate that ubiquitin is highly tolerant to single mutations. We hypothesized that thi…

Author response: Determination of ubiquitin fitness landscapes under different chemical stresses in a classroom setting Open

David Mavor, Kyle A. Barlow, Samuel Thompson, Benjamin A. Barad, Alain R. Bonny , et al. · 2016

Article Figures and data Abstract eLife digest Introduction Results Discussion Materials and methods Data availability References Decision letter Author response Article and author information Metrics Abstract Ubiquitin is essential for eu…

Thermodynamics of Rev–RNA Interactions in HIV-1 Rev–RRE Assembly Open

Bhargavi Jayaraman, David Mavor, John D. Gross, Alan D. Frankel · 2015

The HIV-1 protein Rev facilitates the nuclear export of intron-containing viral mRNAs by recognizing a structured RNA site, the Rev-response-element (RRE), contained in an intron. Rev assembles as a homo-oligomer on the RRE using its α-hel…

Determination of Ubiquitin Fitness Landscapes Under Different Chemical Stresses in a Classroom Setting Open

David Mavor, Kyle A. Barlow, Samuel Thompson, Benjamin A. Barad, Alain R. Bonny , et al. · 2015

Ubiquitination is an essential post-translational regulatory process that can control protein stability, localization, and activity. Ubiquitin is essential for eukaryotic life and is highly conserved, varying in only 3 amino acid positions…

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