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1. Elevated Basal Slippage Mutation Rates among the Canidae

Author:
Ranganathan, Rama,   et al.   ; Laidlaw, Jeffrey; Gelfand, Yevgeniy; Ng, Kar-Wai; Garner, Harold R.; Benson, Gary; Fondon, John W. III.;     Show all 7 Authors
Source:
Journal of heredity 2007 v.98 no.5 pp. 452-460
ISSN:
0022-1503
Subject:
Canidae; carnivores; dogs; genes; humans; mutation; rodents; tandem repeat sequences
Abstract:
... The remarkable responsiveness of dog morphology to selection is a testament to the mutability of mammals. The genetic sources of this morphological variation are largely unknown, but some portion is due to tandem repeat length variation in genes involved in development. Previous analysis of tandem repeats in coding regions of developmental genes revealed fewer interruptions in repeat sequences in ...
DOI:
10.1093/jhered/esm017
PubMed:
17437958

2. Evolvability as a Function of Purifying Selection in TEM-1 β-Lactamase

Author:
Ranganathan, Rama,   et al.   ; Stiffler, Michael A.; Hekstra, Doeke R.;     Show all 3 Authors
Source:
Cell 2015 v.160 pp. 882-892
ISSN:
0092-8674
Subject:
ampicillin; beta-lactamase; cefotaxime; environmental factors; enzyme activity; mutation
Abstract:
... Evolvability—the capacity to generate beneficial heritable variation—is a central property of biological systems. However, its origins and modulation by environmental factors have not been examined systematically. Here, we analyze the fitness effects of all single mutations in TEM-1 β-lactamase (4,997 variants) under selection for the wild-type function (ampicillin resistance) and for a new functi ...
DOI:
10.1016/j.cell.2015.01.035

3. Hot Spots for Allosteric Regulation on Protein Surfaces

Author:
Ranganathan, Rama,   et al.   ; Reynolds, Kimberly A.; McLaughlin, Richard N.;     Show all 3 Authors
Source:
Cell 2011 v.147 no.7 pp. 1564-1575
ISSN:
0092-8674
Subject:
active sites; amino acids; catalytic activity; dihydrofolate reductase; proteins
Abstract:
... Recent work indicates a general architecture for proteins in which sparse networks of physically contiguous and coevolving amino acids underlie basic aspects of structure and function. These networks, termed sectors, are spatially organized such that active sites are linked to many surface sites distributed throughout the structure. Using the metabolic enzyme dihydrofolate reductase as a model sys ...
DOI:
10.1016/j.cell.2011.10.049
PubMed:
22196731
PubMed Central:
PMC3414429

4. Origins of Allostery and Evolvability in Proteins: A Case Study

Author:
Ranganathan, Rama,   et al.   ; Raman, Arjun S.; White, K. Ian;     Show all 3 Authors
Source:
Cell 2016 v.166 pp. 468-480
ISSN:
0092-8674
Subject:
active sites; amino acids; case studies; evolutionary adaptation; ligands; mutation; phenotype; proteins
Abstract:
... Proteins display the capacity for adaptation to new functions, a property critical for evolvability. But what structural principles underlie the capacity for adaptation? Here, we show that adaptation to a physiologically distinct class of ligand specificity in a PSD95, DLG1, ZO-1 (PDZ) domain preferentially occurs through class-bridging intermediate mutations located distant from the ligand-bindin ...
DOI:
10.1016/j.cell.2016.05.047

5. Putting Evolution to Work

Author:
Ranganathan, Rama
Source:
Cell 2018 v.175 no.6 pp. 1449-1451
ISSN:
0092-8674
Subject:
Nobel Prize; chemistry; evolution; protein engineering
Abstract:
... This year, the Nobel Prize in Chemistry was awarded to three pioneering scientists who applied laboratory evolution for protein engineering: Frances Arnold, George P. Smith, and Sir Gregory P. Winter. This approach has had major impact in various applications and inspires the search for the general principles of design through evolution. ...
DOI:
10.1016/j.cell.2018.11.015

6. Signal transduction pathway of TonB-dependent transporters

Author:
Ranganathan, Rama,   et al.   ; Ferguson, Andrew D.; Amezcua, Carlos A.; Halabi, Najeeb M.; Chelliah, Yogarany; Rosen, Michael K.; Deisenhofer, Johann;     Show all 7 Authors
Source:
Proceedings of the National Academy of Sciences of the United States of America 2007 v.104 no.2 pp. 513-518
ISSN:
0027-8424
Subject:
cell membranes; citrates; regulatory proteins; signal transduction; statistical analysis; transcriptional activation; transporters
Abstract:
... Transcription of the ferric citrate import system is regulated by ferric citrate binding to the outer membrane transporter FecA. A signal indicating transporter occupancy is relayed across the outer membrane to energy-transducing and regulatory proteins embedded in the cytoplasmic membrane. Because transcriptional activation is not coupled to ferric citrate import, an allosteric mechanism underlie ...
DOI:
10.1073/pnas.0609887104
PubMed:
17197416
PubMed Central:
PMC1760641

7. Surface Sites for Engineering Allosteric Control in Proteins

Author:
Ranganathan, Rama,   et al.   ; Lee, Jeeyeon; Natarajan, Madhusudan; Nashine, Vishal C.; Socolich, Michael; Vo, Tina; Russ, William P.; Benkovic, Stephen J.;     Show all 8 Authors
Source:
Science 2008 v.322 no.5900 pp. 438-442
ISSN:
0036-8075
Subject:
Escherichia coli; amino acids; catalytic activity; dihydrofolate reductase; engineering; recombinant fusion proteins; statistical analysis
Abstract:
... Statistical analyses of protein families reveal networks of coevolving amino acids that functionally link distantly positioned functional surfaces. Such linkages suggest a concept for engineering allosteric control into proteins: The intramolecular networks of two proteins could be joined across their surface sites such that the activity of one protein might control the activity of the other. We t ...
DOI:
10.1126/science.1159052
PubMed:
18927392
PubMed Central:
PMC3071530

8. Systems analysis of the single photon response in invertebrate photoreceptors

Author:
Ranganathan, Rama,   et al.   ; Pumir, Alain; Graves, Jennifer; Shraiman, Boris I.;     Show all 4 Authors
Source:
Proceedings of the National Academy of Sciences of the United States of America 2008 v.105 no.30 pp. 10354-10359
ISSN:
0027-8424
Subject:
ion channels; calcium; G-proteins; phototransduction; electrophysiology; Drosophila melanogaster; photoreceptors; light
Abstract:
... Photoreceptors of Drosophila compound eye employ a G protein-mediated signaling pathway that transduces single photons into transient electrical responses called "quantum bumps" (QB). Although most of the molecular components of this pathway are already known, the system-level understanding of the mechanism of QB generation has remained elusive. Here, we present a quantitative model explaining how ...
DOI:
10.1073/pnas.0711884105
PubMed:
18653755
PubMed Central:
PMC2492478