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Title: Structural Evidence for Dimer-Interface-Driven Regulation of the Type II Cysteine Desulfurase, SufS

Abstract

SufS is a type II cysteine desulfurase and acts as the initial step in the Suf Fe–S cluster assembly pathway. In Escherichia coli, this pathway is utilized under conditions of oxidative stress and is resistant to reactive oxygen species. Mechanistically, this means SufS must shift between protecting a covalent persulfide intermediate and making it available for transfer to the next protein partner in the pathway, SufE. Here, we report five X-ray crystal structures of SufS including a new structure of SufS containing an inward-facing persulfide intermediate on C364. Additional structures of SufS variants with substitutions at the dimer interface show changes in dimer geometry and suggest a conserved β-hairpin structure plays a role in mediating interactions with SufE. Here, these new structures, along with previous HDX-MS and biochemical data, identify an interaction network capable of communication between active-sites of the SufS dimer coordinating the shift between desulfurase and transpersulfurase activities.

Authors:
 [1];  [1]; ORCiD logo [2]; ORCiD logo [1]
  1. Univ. of Alabama, Tuscaloosa, AL (United States)
  2. Univ. of South Carolina, Columbia, SC (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health
OSTI Identifier:
1494761
Grant/Contract Number:  
W-31-109-Eng-38; S10_RR25528; S10_RR028976; GM112919
Resource Type:
Accepted Manuscript
Journal Name:
Biochemistry
Additional Journal Information:
Journal Volume: 58; Journal Issue: 6; Journal ID: ISSN 0006-2960
Publisher:
American Chemical Society (ACS)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; interfaces; peptides and proteins; monomers; crystal structure; oligomers

Citation Formats

Dunkle, Jack A., Bruno, Michael R., Outten, F. Wayne, and Frantom, Patrick A. Structural Evidence for Dimer-Interface-Driven Regulation of the Type II Cysteine Desulfurase, SufS. United States: N. p., 2018. Web. doi:10.1021/acs.biochem.8b01122.
Dunkle, Jack A., Bruno, Michael R., Outten, F. Wayne, & Frantom, Patrick A. Structural Evidence for Dimer-Interface-Driven Regulation of the Type II Cysteine Desulfurase, SufS. United States. https://doi.org/10.1021/acs.biochem.8b01122
Dunkle, Jack A., Bruno, Michael R., Outten, F. Wayne, and Frantom, Patrick A. Thu . "Structural Evidence for Dimer-Interface-Driven Regulation of the Type II Cysteine Desulfurase, SufS". United States. https://doi.org/10.1021/acs.biochem.8b01122. https://www.osti.gov/servlets/purl/1494761.
@article{osti_1494761,
title = {Structural Evidence for Dimer-Interface-Driven Regulation of the Type II Cysteine Desulfurase, SufS},
author = {Dunkle, Jack A. and Bruno, Michael R. and Outten, F. Wayne and Frantom, Patrick A.},
abstractNote = {SufS is a type II cysteine desulfurase and acts as the initial step in the Suf Fe–S cluster assembly pathway. In Escherichia coli, this pathway is utilized under conditions of oxidative stress and is resistant to reactive oxygen species. Mechanistically, this means SufS must shift between protecting a covalent persulfide intermediate and making it available for transfer to the next protein partner in the pathway, SufE. Here, we report five X-ray crystal structures of SufS including a new structure of SufS containing an inward-facing persulfide intermediate on C364. Additional structures of SufS variants with substitutions at the dimer interface show changes in dimer geometry and suggest a conserved β-hairpin structure plays a role in mediating interactions with SufE. Here, these new structures, along with previous HDX-MS and biochemical data, identify an interaction network capable of communication between active-sites of the SufS dimer coordinating the shift between desulfurase and transpersulfurase activities.},
doi = {10.1021/acs.biochem.8b01122},
journal = {Biochemistry},
number = 6,
volume = 58,
place = {United States},
year = {Thu Dec 20 00:00:00 EST 2018},
month = {Thu Dec 20 00:00:00 EST 2018}
}

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Works referenced in this record:

Fe-S Cluster Assembly Pathways in Bacteria
journal, March 2008

  • Ayala-Castro, C.; Saini, A.; Outten, F. W.
  • Microbiology and Molecular Biology Reviews, Vol. 72, Issue 1
  • DOI: 10.1128/MMBR.00034-07

Shared-intermediates in the biosynthesis of thio-cofactors: Mechanism and functions of cysteine desulfurases and sulfur acceptors
journal, June 2015

  • Black, Katherine A.; Dos Santos, Patricia C.
  • Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1853, Issue 6
  • DOI: 10.1016/j.bbamcr.2014.10.018

Mechanism for the Desulfurization of L-Cysteine Catalyzed by the nifS Gene Product
journal, April 1994

  • Zheng, Limin; White, Robert H.; Cash, Valerie L.
  • Biochemistry, Vol. 33, Issue 15
  • DOI: 10.1021/bi00181a031

Kinetic and Structural Characterization of Slr0077/SufS, the Essential Cysteine Desulfurase from Synechocystis sp. PCC 6803 ,
journal, September 2004

  • Tirupati, Bhramara; Vey, Jessica Lynn; Drennan, Catherine L.
  • Biochemistry, Vol. 43, Issue 38
  • DOI: 10.1021/bi0491447

Kinetic Analysis of Cysteine Desulfurase CD0387 from Synechocystis sp. PCC 6803: Formation of the Persulfide Intermediate
journal, December 2009

  • Behshad, Elham; Bollinger, J. Martin
  • Biochemistry, Vol. 48, Issue 50
  • DOI: 10.1021/bi802161u

Crystal structure of a NifS-like protein from Thermotoga maritima: implications for iron sulphur cluster assembly
journal, March 2000

  • Kaiser, Jens T.; Clausen, Tim; Bourenkow, Gleb P.
  • Journal of Molecular Biology, Vol. 297, Issue 2
  • DOI: 10.1006/jmbi.2000.3581

(IscS-IscU) 2 Complex Structures Provide Insights into Fe 2 S 2 Biogenesis and Transfer
journal, April 2012

  • Marinoni, Elodie N.; de Oliveira, Jaim S.; Nicolet, Yvain
  • Angewandte Chemie International Edition, Vol. 51, Issue 22
  • DOI: 10.1002/anie.201201708

Structural bases for the interaction of frataxin with the central components of iron–sulphur cluster assembly
journal, October 2010

  • Prischi, Filippo; Konarev, Petr V.; Iannuzzi, Clara
  • Nature Communications, Vol. 1, Issue 1
  • DOI: 10.1038/ncomms1097

Structure of a NifS Homologue:  X-ray Structure Analysis of CsdB, an Escherichia coli Counterpart of Mammalian Selenocysteine Lyase ,
journal, February 2000

  • Fujii, Tomomi; Maeda, Masaki; Mihara, Hisaaki
  • Biochemistry, Vol. 39, Issue 6
  • DOI: 10.1021/bi991732a

The SufE Protein and the SufBCD Complex Enhance SufS Cysteine Desulfurase Activity as Part of a Sulfur Transfer Pathway for Fe-S Cluster Assembly in Escherichia coli
journal, August 2003

  • Outten, F. Wayne; Wood, Matthew J.; Muñoz, F. Michael
  • Journal of Biological Chemistry, Vol. 278, Issue 46
  • DOI: 10.1074/jbc.M308004200

Escherichia coli SufE Sulfur Transfer Protein Modulates the SufS Cysteine Desulfurase through Allosteric Conformational Dynamics
journal, November 2013

  • Singh, Harsimran; Dai, Yuyuan; Outten, F. Wayne
  • Journal of Biological Chemistry, Vol. 288, Issue 51
  • DOI: 10.1074/jbc.M113.525709

SufE D74R Substitution Alters Active Site Loop Dynamics To Further Enhance SufE Interaction with the SufS Cysteine Desulfurase
journal, July 2015


Kinetic Analysis of the Bisubstrate Cysteine Desulfurase SufS from Bacillus subtilis
journal, October 2010

  • Selbach, Bruna; Earles, Emily; Dos Santos, Patricia C.
  • Biochemistry, Vol. 49, Issue 40
  • DOI: 10.1021/bi101358k

The E. coli SufS-SufE sulfur transfer system is more resistant to oxidative stress than IscS-IscU
journal, October 2012


Protected Sulfur Transfer Reactions by the Escherichia coli Suf System
journal, May 2013

  • Selbach, Bruna P.; Pradhan, Pradyumna K.; Dos Santos, Patricia C.
  • Biochemistry, Vol. 52, Issue 23
  • DOI: 10.1021/bi4001479

[20] Processing of X-ray diffraction data collected in oscillation mode
book, January 1997


PHENIX: a comprehensive Python-based system for macromolecular structure solution
journal, January 2010

  • Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor
  • Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2, p. 213-221
  • DOI: 10.1107/S0907444909052925

Fast native-SAD phasing for routine macromolecular structure determination
journal, December 2014

  • Weinert, Tobias; Olieric, Vincent; Waltersperger, Sandro
  • Nature Methods, Vol. 12, Issue 2
  • DOI: 10.1038/nmeth.3211

Structures from Anomalous Diffraction of Native Biological Macromolecules
journal, May 2012


Linking Crystallographic Model and Data Quality
journal, May 2012


Using Sequence Similarity Networks for Visualization of Relationships Across Diverse Protein Superfamilies
journal, February 2009


Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks
journal, November 2003


Enzyme Function Initiative-Enzyme Similarity Tool (EFI-EST): A web tool for generating protein sequence similarity networks
journal, August 2015

  • Gerlt, John A.; Bouvier, Jason T.; Davidson, Daniel B.
  • Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1854, Issue 8
  • DOI: 10.1016/j.bbapap.2015.04.015

MUSCLE: multiple sequence alignment with high accuracy and high throughput
journal, March 2004

  • Edgar, R. C.
  • Nucleic Acids Research, Vol. 32, Issue 5, p. 1792-1797
  • DOI: 10.1093/nar/gkh340

Two WXXF-based motifs in NECAPs define the specificity of accessory protein binding to AP-1 and AP-2
journal, September 2004

  • Ritter, Brigitte; Denisov, Alexei Yu; Philie, Jacynthe
  • The EMBO Journal, Vol. 23, Issue 19
  • DOI: 10.1038/sj.emboj.7600378

Structural Changes during Cysteine Desulfurase CsdA and Sulfur Acceptor CsdE Interactions Provide Insight into the trans -Persulfuration
journal, August 2013


Interplay between Oxygen and Fe–S Cluster Biogenesis: Insights from the Suf Pathway
journal, September 2014

  • Boyd, Eric S.; Thomas, Khaleh M.; Dai, Yuyuan
  • Biochemistry, Vol. 53, Issue 37
  • DOI: 10.1021/bi500488r

Works referencing / citing this record:

Direct observation of intermediates in the SufS cysteine desulfurase reaction reveals functional roles of conserved active-site residues
journal, June 2019

  • Blahut, Matthew; Wise, Courtney E.; Bruno, Michael R.
  • Journal of Biological Chemistry, Vol. 294, Issue 33
  • DOI: 10.1074/jbc.ra119.009471

Snapshots of PLP‐substrate and PLP‐product external aldimines as intermediates in two types of cysteine desulfurase enzymes
journal, October 2019

  • Nakamura, Ryosuke; Hikita, Masahide; Ogawa, Shoko
  • The FEBS Journal, Vol. 287, Issue 6
  • DOI: 10.1111/febs.15081

A conserved asparagine in a ubiquitin‐conjugating enzyme positions the substrate for nucleophilic attack
journal, May 2019

  • Jones, Walker M.; Davis, Aaron G.; Wilson, R. Hunter
  • Journal of Computational Chemistry, Vol. 40, Issue 22
  • DOI: 10.1002/jcc.25852

The SUF system: an ABC ATPase-dependent protein complex with a role in Fe–S cluster biogenesis
journal, November 2019