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Title: H/D exchange mass spectrometry and statistical coupling analysis reveal a role for allostery in a ferredoxin-dependent bifurcating transhydrogenase catalytic cycle

Abstract

Recent investigations into ferredoxin-dependent transhydrogenases, a class of enzymes responsible for electron transport, have highlighted the biological importance of flavin-based electron bifurcation (FBEB). FBEB generates biomolecules with very low reduction potential by coupling the oxidation of an electron donor with intermediate potential to the reduction of high and low potential molecules. Bifurcating systems can generate biomolecules with very low reduction potentials, such as reduced ferredoxin (Fd), from species such as NADPH. Metabolic systems that use bifurcation are more efficient and confer a competitive advantage for the organisms that harbor them. Structural models are now available for two NADH-dependent ferredoxin-NADP+ oxidoreductase (Nfn) complexes. These models, together with spectroscopic studies, have provided considerable insight into the catalytic process of FBEB. However, much about the mechanism and regulation of these multi-subunit proteins remains unclear. Using hydrogen/deuterium exchange mass spectrometry (HDX-MS) and statistical coupling analysis (SCA), we identified in this work specific pathways of communication within the model FBEB system, Nfn from Pyrococus furiosus, under conditions at each step of the catalytic cycle. HDX-MS revealed evidence for allosteric coupling across protein subunits upon nucleotide and ferredoxin binding. SCA uncovered a network of co-evolving residues that can provide connectivity across the complex. Together, the HDX-MSmore » and SCA data show that protein allostery occurs across the ensemble of iron-sulfur cofactors and ligand binding sites using specific pathways that connect domains allowing them to function as dynamically coordinated units.« less

Authors:
 [1];  [1];  [1];  [1];  [2];  [2];  [2];  [3];  [1];  [1]
+ Show Author Affiliations
  1. Montana State Univ., Bozeman, MT (United States)
  2. Univ. of Georgia, Athens, GA (United States)
  3. Washington State Univ., Pullman, WA (United States)
Publication Date:
Research Org.:
Energy Frontier Research Centers (EFRC) (United States). Center for Biological Electron Transfer and Catalysis (BETCy)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)
OSTI Identifier:
1469904
Alternate Identifier(s):
OSTI ID: 1549363
Grant/Contract Number:  
SC0012518; P20GM103474
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Biochimica et Biophysica Acta - General Subjects
Additional Journal Information:
Journal Volume: 1862; Journal Issue: 1; Related Information: BETCy partners with Montana State University (lead); Arizona State University; National Renewable Energy Laboratory; University of Georgia; University of Kentucky; University of Washington; Utah State University; Journal ID: ISSN 0304-4165
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; solar (fuels); biofuels (including algae and biomass); bio-inspired; hydrogen and fuel cells; HDX-MS; SCA; Electron bifurcation; Allostery; Ferredoxin-dependent transhydrogenase; Flavin-based electron bifurcation

Citation Formats

Berry, Luke, Poudel, Saroj, Tokmina-Lukaszewska, Monika, Colman, Daniel R., Nguyen, Diep M. N., Schut, Gerrit J., Adams, Michael W. W., Peters, John W., Boyd, Eric S., and Bothner, Brian. H/D exchange mass spectrometry and statistical coupling analysis reveal a role for allostery in a ferredoxin-dependent bifurcating transhydrogenase catalytic cycle. United States: N. p., 2017. Web. doi:10.1016/j.bbagen.2017.10.002.
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Berry, Luke, Poudel, Saroj, Tokmina-Lukaszewska, Monika, Colman, Daniel R., Nguyen, Diep M. N., Schut, Gerrit J., Adams, Michael W. W., Peters, John W., Boyd, Eric S., & Bothner, Brian. H/D exchange mass spectrometry and statistical coupling analysis reveal a role for allostery in a ferredoxin-dependent bifurcating transhydrogenase catalytic cycle. United States. https://doi.org/10.1016/j.bbagen.2017.10.002
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Berry, Luke, Poudel, Saroj, Tokmina-Lukaszewska, Monika, Colman, Daniel R., Nguyen, Diep M. N., Schut, Gerrit J., Adams, Michael W. W., Peters, John W., Boyd, Eric S., and Bothner, Brian. 2017. "H/D exchange mass spectrometry and statistical coupling analysis reveal a role for allostery in a ferredoxin-dependent bifurcating transhydrogenase catalytic cycle". United States. https://doi.org/10.1016/j.bbagen.2017.10.002. https://www.osti.gov/servlets/purl/1469904.
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@article{osti_1469904,
title = {H/D exchange mass spectrometry and statistical coupling analysis reveal a role for allostery in a ferredoxin-dependent bifurcating transhydrogenase catalytic cycle},
author = {Berry, Luke and Poudel, Saroj and Tokmina-Lukaszewska, Monika and Colman, Daniel R. and Nguyen, Diep M. N. and Schut, Gerrit J. and Adams, Michael W. W. and Peters, John W. and Boyd, Eric S. and Bothner, Brian},
abstractNote = {Recent investigations into ferredoxin-dependent transhydrogenases, a class of enzymes responsible for electron transport, have highlighted the biological importance of flavin-based electron bifurcation (FBEB). FBEB generates biomolecules with very low reduction potential by coupling the oxidation of an electron donor with intermediate potential to the reduction of high and low potential molecules. Bifurcating systems can generate biomolecules with very low reduction potentials, such as reduced ferredoxin (Fd), from species such as NADPH. Metabolic systems that use bifurcation are more efficient and confer a competitive advantage for the organisms that harbor them. Structural models are now available for two NADH-dependent ferredoxin-NADP+ oxidoreductase (Nfn) complexes. These models, together with spectroscopic studies, have provided considerable insight into the catalytic process of FBEB. However, much about the mechanism and regulation of these multi-subunit proteins remains unclear. Using hydrogen/deuterium exchange mass spectrometry (HDX-MS) and statistical coupling analysis (SCA), we identified in this work specific pathways of communication within the model FBEB system, Nfn from Pyrococus furiosus, under conditions at each step of the catalytic cycle. HDX-MS revealed evidence for allosteric coupling across protein subunits upon nucleotide and ferredoxin binding. SCA uncovered a network of co-evolving residues that can provide connectivity across the complex. Together, the HDX-MS and SCA data show that protein allostery occurs across the ensemble of iron-sulfur cofactors and ligand binding sites using specific pathways that connect domains allowing them to function as dynamically coordinated units.},
doi = {10.1016/j.bbagen.2017.10.002},
url = {https://www.osti.gov/biblio/1469904}, journal = {Biochimica et Biophysica Acta - General Subjects},
issn = {0304-4165},
number = 1,
volume = 1862,
place = {United States},
year = {Fri Oct 06 00:00:00 EDT 2017},
month = {Fri Oct 06 00:00:00 EDT 2017}
}
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Journal Article:
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Publisher's Version of Record
https://doi.org/10.1016/j.bbagen.2017.10.002
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Cited by: 19 works
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Works referenced in this record:

Energy conservation via electron bifurcating ferredoxin reduction and proton/Na+ translocating ferredoxin oxidation
journal, February 2013

Energy Conservation via Electron-Transferring Flavoprotein in Anaerobic Bacteria
journal, November 2007

Insights into Flavin-based Electron Bifurcation via the NADH-dependent Reduced Ferredoxin:NADP Oxidoreductase Structure
journal, July 2015

Mechanistic insights into energy conservation by flavin-based electron bifurcation
journal, April 2017

Two functionally distinct NADP + -dependent ferredoxin oxidoreductases maintain the primary redox balance of Pyrococcus furiosus
journal, July 2017

Conformational changes in proteins probed by hydrogen-exchange electrospray-ionization mass spectrometry
journal, April 1991

Hydrogen exchange mass spectrometry: what is it and what can it tell us?
journal, March 2010

Structural Basis for Activation of Calcineurin by Calmodulin
journal, January 2012

Partial cooperative unfolding in proteins as observed by hydrogen exchange mass spectrometry
journal, March 2013

Allosteric regulation and catalysis emerge via a common route
journal, July 2008

Protein Sectors: Evolutionary Units of Three-Dimensional Structure
journal, August 2009

Methods for the analysis of high precision differential hydrogen–deuterium exchange data
journal, April 2011

Fast, scalable generation of high‐quality protein multiple sequence alignments using Clustal Omega
journal, January 2011

UCSF Chimera?A visualization system for exploratory research and analysis
journal, January 2004

Cytoscape 2.8: new features for data integration and network visualization
journal, December 2010

Computing topological parameters of biological networks
journal, November 2007

Conformational Equilibria and Rates of Localized Motion within Hepatitis B Virus Capsids
journal, January 2008

Biological insights from hydrogen exchange mass spectrometry
journal, June 2013

Analysis of Protein Conformation and Dynamics by Hydrogen/Deuterium Exchange MS
journal, October 2009

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    Works referencing / citing this record:

    On the nature of organic and inorganic centers that bifurcate electrons, coupling exergonic and endergonic oxidation–reduction reactions
    journal, January 2018

    Origin and Evolution of Flavin-Based Electron Bifurcating Enzymes
    journal, August 2018

    Residue-Level Allostery Propagates through the Effective Coarse-Grained Hessian
    journal, April 2020

    Origin and Evolution of Flavin-Based Electron Bifurcating Enzymes
    journal, August 2018

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