Solution structure for an Encephalitozoon cuniculi adrenodoxin-like protein in the oxidized state
Abstract
Encephalitozoon cuniculi is a unicellular, obligate intracellular eukaryotic parasite in the Microsporidia family and one of the agents responsible for microsporidosis infections in humans. Like most Microsporidia, the genome of E. cuniculi is markedly reduced and the organism contains mitochondria-like organelles called mitosomes instead of mitochondria. Here we report the solution NMR structure for a protein physically associated with mitosome-like organelles in E. cuniculi, the 128-residue, adrenodoxin-like protein Ec-Adx (UniProt ID Q8SV19) in the [2Fe-2S] ferredoxin superfamily. Oxidized Ec-Adx contains a mixed four-strand β-sheet, β2-β1-β4-β3 (↓↑↑↓), loosely encircled by three α-helices and two 310-helices. This fold is similar to the structure observed in other adrenodoxin and adrenodoxin-like proteins except for the absence of a fifth anti-parallel β-strand next to β3 and the position of α3. Cross peaks are missing or cannot be unambiguously assigned for 20 amide resonances in the 1H-15N HSQC spectrum of Ec-Adx. These missing residues are clustered primarily in two regions, G48-V61 and L94-L98, containing the four cysteine residues predicted to ligate the paramagnetic [2Fe-2S] cluster. Missing amide resonances in 1H-15N HSQC spectra are detrimental to NMR-based solution structure calculations because 1H-1H NOE restraints are absent (glass half-empty) and this may account for the absent β-strand (β5)more »
- Authors:
-
- Univ. of Washington, Seattle, WA (United States). Dept. of Medicine, Division of Allergy and Infectious Disease, Center for Emerging and Remerging Infectious Disease
- Univ. of Washington, Seattle, WA (United States). Dept. of Medicine, Division of Allergy and Infectious Disease, Center for Emerging and Remerging Infectious Disease; Seattle Structural Genomics Center for Infectious Diseases (United States)
- Seattle Structural Genomics Center for Infectious Diseases (United States); Seattle Children's Research Inst., Seattle, WA (United States). Center for Global Infectious Disease Research
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Seattle Children's Research Institute (United States); Univ. of Washington, Seattle, WA (United States). Dept. of Medicine, Division of Allergy and Infectious Disease, Center for Emerging and Remerging Infectious Disease; Seattle Structural Genomics Center for Infectious Diseases (United States)
- Seattle Structural Genomics Center for Infectious Diseases (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Univ. of Washington, Seattle, WA (United States)
- Publication Date:
- Research Org.:
- Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1599908
- Report Number(s):
- PNNL-SA-150252
Journal ID: ISSN 0961-8368
- Grant/Contract Number:
- AC05-76RL01830; HHSH27220120025C; HHSN272200700057C; HHSN272201700059C
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Protein Science
- Additional Journal Information:
- Journal Volume: 29; Journal Issue: 3; Journal ID: ISSN 0961-8368
- Publisher:
- The Protein Society
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Shaheen, Shareef, Barrett, Kayleigh F., Subramanian, Sandhya, Arnold, Samuel L. M., Laureanti, Joseph A., Myler, Peter J., Van Voorhis, Wesley C., and Buchko, Garry W. Solution structure for an Encephalitozoon cuniculi adrenodoxin-like protein in the oxidized state. United States: N. p., 2020.
Web. doi:10.1002/pro.3818.
Shaheen, Shareef, Barrett, Kayleigh F., Subramanian, Sandhya, Arnold, Samuel L. M., Laureanti, Joseph A., Myler, Peter J., Van Voorhis, Wesley C., & Buchko, Garry W. Solution structure for an Encephalitozoon cuniculi adrenodoxin-like protein in the oxidized state. United States. https://doi.org/10.1002/pro.3818
Shaheen, Shareef, Barrett, Kayleigh F., Subramanian, Sandhya, Arnold, Samuel L. M., Laureanti, Joseph A., Myler, Peter J., Van Voorhis, Wesley C., and Buchko, Garry W. Mon .
"Solution structure for an Encephalitozoon cuniculi adrenodoxin-like protein in the oxidized state". United States. https://doi.org/10.1002/pro.3818. https://www.osti.gov/servlets/purl/1599908.
@article{osti_1599908,
title = {Solution structure for an Encephalitozoon cuniculi adrenodoxin-like protein in the oxidized state},
author = {Shaheen, Shareef and Barrett, Kayleigh F. and Subramanian, Sandhya and Arnold, Samuel L. M. and Laureanti, Joseph A. and Myler, Peter J. and Van Voorhis, Wesley C. and Buchko, Garry W.},
abstractNote = {Encephalitozoon cuniculi is a unicellular, obligate intracellular eukaryotic parasite in the Microsporidia family and one of the agents responsible for microsporidosis infections in humans. Like most Microsporidia, the genome of E. cuniculi is markedly reduced and the organism contains mitochondria-like organelles called mitosomes instead of mitochondria. Here we report the solution NMR structure for a protein physically associated with mitosome-like organelles in E. cuniculi, the 128-residue, adrenodoxin-like protein Ec-Adx (UniProt ID Q8SV19) in the [2Fe-2S] ferredoxin superfamily. Oxidized Ec-Adx contains a mixed four-strand β-sheet, β2-β1-β4-β3 (↓↑↑↓), loosely encircled by three α-helices and two 310-helices. This fold is similar to the structure observed in other adrenodoxin and adrenodoxin-like proteins except for the absence of a fifth anti-parallel β-strand next to β3 and the position of α3. Cross peaks are missing or cannot be unambiguously assigned for 20 amide resonances in the 1H-15N HSQC spectrum of Ec-Adx. These missing residues are clustered primarily in two regions, G48-V61 and L94-L98, containing the four cysteine residues predicted to ligate the paramagnetic [2Fe-2S] cluster. Missing amide resonances in 1H-15N HSQC spectra are detrimental to NMR-based solution structure calculations because 1H-1H NOE restraints are absent (glass half-empty) and this may account for the absent β-strand (β5) and the position of α3 in oxidized Ec-Adx. On the other hand, the missing amide resonances unambiguously identify the presence, and immediate environment, of the paramagnetic [2Fe-2S] cluster in oxidized Ec-Adx (glass half-full).},
doi = {10.1002/pro.3818},
journal = {Protein Science},
number = 3,
volume = 29,
place = {United States},
year = {Mon Jan 20 00:00:00 EST 2020},
month = {Mon Jan 20 00:00:00 EST 2020}
}
Web of Science
Works referenced in this record:
Microsporidian mitosomes retain elements of the general mitochondrial targeting system
journal, October 2006
- Burri, L.; Williams, B. A. P.; Bursac, D.
- Proceedings of the National Academy of Sciences, Vol. 103, Issue 43
Distinct Localization Patterns of Two Putative Mitochondrial Proteins in the Microsporidian Encephalitozoon cuniculi
journal, March 2008
- Williams, Bryony A. P.; Cali, Ann; Takvorian, Peter M.
- Journal of Eukaryotic Microbiology, Vol. 55, Issue 2
Protein targeting in parasites with cryptic mitochondria
journal, March 2007
- Burri, Lena; Keeling, Patrick J.
- International Journal for Parasitology, Vol. 37, Issue 3-4
Backbone chemical shift assignments for Xanthomonas campestris peroxiredoxin Q in the reduced and oxidized states: a dramatic change in backbone dynamics
journal, September 2015
- Buchko, Garry W.; Perkins, Arden; Parsonage, Derek
- Biomolecular NMR Assignments, Vol. 10, Issue 1
Zoonotic Potential of the Microsporidia
journal, July 2005
- Mathis, A.; Weber, R.; Deplazes, P.
- Clinical Microbiology Reviews, Vol. 18, Issue 3
Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct roles in steroidogenesis, heme, and Fe/S cluster biosynthesis
journal, June 2010
- Sheftel, A. D.; Stehling, O.; Pierik, A. J.
- Proceedings of the National Academy of Sciences, Vol. 107, Issue 26
Structural/Functional Properties of Human NFU1, an Intermediate [4Fe-4S] Carrier in Human Mitochondrial Iron-Sulfur Cluster Biogenesis
journal, December 2016
- Cai, Kai; Liu, Gaohua; Frederick, Ronnie O.
- Structure, Vol. 24, Issue 12
Iron-Sulfur Clusters: Nature's Modular, Multipurpose Structures
journal, August 1997
- Beinert, H.
- Science, Vol. 277, Issue 5326
Refined X-ray Structures of the Oxidized, at 1.3 Å, and Reduced, at 1.17 Å, [2Fe−2S] Ferredoxin from the Cyanobacterium Anabaena PCC7119 Show Redox-Linked Conformational Changes †
journal, November 1999
- Morales, Renaud; Charon, Marie-Hélène; Hudry-Clergeon, Gilbert
- Biochemistry, Vol. 38, Issue 48
Microsporidiosis Acquired Through Solid Organ Transplantation: A Public Health Investigation
journal, February 2014
- Hocevar, Susan N.; Paddock, Christopher D.; Spak, Cedric W.
- Annals of Internal Medicine, Vol. 160, Issue 4
An NMR approach to structural proteomics
journal, February 2002
- Yee, A.; Chang, X.; Pineda-Lucena, A.
- Proceedings of the National Academy of Sciences, Vol. 99, Issue 4
TALOS+: a hybrid method for predicting protein backbone torsion angles from NMR chemical shifts
journal, June 2009
- Shen, Yang; Delaglio, Frank; Cornilescu, Gabriel
- Journal of Biomolecular NMR, Vol. 44, Issue 4
Function and biogenesis of iron–sulphur proteins
journal, August 2009
- Lill, Roland
- Nature, Vol. 460, Issue 7257
Five Questions about Microsporidia
journal, September 2009
- Keeling, Patrick
- PLoS Pathogens, Vol. 5, Issue 9
Microsporidia: accumulating molecular evidence that a group of amitochondriate and suspectedly primitive eukaryotes are just curious fungi
journal, April 2000
- Van de Peer, Yves; Ben Ali, Abdelghani; Meyer, Axel
- Gene, Vol. 246, Issue 1-2
Highly divergent mitochondrion-related organelles in anaerobic parasitic protozoa
journal, May 2014
- Makiuchi, Takashi; Nozaki, Tomoyoshi
- Biochimie, Vol. 100
Deleterious mutation in FDX1L gene is associated with a novel mitochondrial muscle myopathy
journal, November 2013
- Spiegel, Ronen; Saada, Ann; Halvardson, Jonatan
- European Journal of Human Genetics, Vol. 22, Issue 7
Analysis of the Beta-Tubulin Gene and Morphological Changes of the Microsporidium Anncaliia algerae both Suggest Albendazole Sensitivity
journal, September 2014
- Santiana, Marianita; Pau, Cyrilla; Takvorian, Peter M.
- Journal of Eukaryotic Microbiology, Vol. 62, Issue 1
Evaluating protein structures determined by structural genomics consortia
journal, December 2006
- Bhattacharya, Aneerban; Tejero, Roberto; Montelione, Gaetano T.
- Proteins: Structure, Function, and Bioinformatics, Vol. 66, Issue 4
Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi
journal, November 2001
- Katinka, Michaël D.; Duprat, Simone; Cornillot, Emmanuel
- Nature, Vol. 414, Issue 6862
Tools for integrated sequence-structure analysis with UCSF Chimera
journal, July 2006
- Meng, Elaine C.; Pettersen, Eric F.; Couch, Gregory S.
- BMC Bioinformatics, Vol. 7, Issue 1
Adrenodoxin-A versatile ferredoxin
journal, May 2012
- Ewen, Kerstin Maria; Ringle, Michael; Bernhardt, Rita
- IUBMB Life, Vol. 64, Issue 6
Adrenodoxin: Structure, stability, and electron transfer properties
journal, January 2000
- Grinberg, Asya V.; Hannemann, Frank; Schiffler, Burkhard
- Proteins: Structure, Function, and Genetics, Vol. 40, Issue 4
Interactions of Human Nucleotide Excision Repair Protein XPA with DNA and RPA70ΔC327: Chemical Shift Mapping and 15 N NMR Relaxation Studies †
journal, November 1999
- Buchko, Garry W.; Daughdrill, Gary W.; de Lorimier, Robert
- Biochemistry, Vol. 38, Issue 46
Cellular Assays for Ferredoxins: A Strategy for Understanding Electron Flow through Protein Carriers That Link Metabolic Pathways
journal, December 2016
- Atkinson, Joshua T.; Campbell, Ian; Bennett, George N.
- Biochemistry, Vol. 55, Issue 51
Therapeutic strategies for human microsporidia infections
journal, June 2005
- Didier, Elizabeth S.; Maddry, Joseph A.; Brindley, Paul J.
- Expert Review of Anti-infective Therapy, Vol. 3, Issue 3
The Tertiary Structure of Full-Length Bovine Adrenodoxin Suggests Functional Dimers
journal, January 2000
- Pikuleva, Irina A.; Tesh, Kris; Waterman, Michael R.
- Archives of Biochemistry and Biophysics, Vol. 373, Issue 1
A New Electron Transport Mechanism in Mitochondrial Steroid Hydroxylase Systems Based on Structural Changes upon the Reduction of Adrenodoxin †
journal, June 2002
- Beilke, Dirk; Weiss, Roland; Löhr, Frank
- Biochemistry, Vol. 41, Issue 25
Functional reconstitution of mitochondrial Fe/S cluster synthesis on Isu1 reveals the involvement of ferredoxin
journal, October 2014
- Webert, Holger; Freibert, Sven-Andreas; Gallo, Angelo
- Nature Communications, Vol. 5, Issue 1
Reduced-dimensionality NMR spectroscopy for high-throughput protein resonance assignment
journal, June 2002
- Szyperski, T.; Yeh, D. C.; Sukumaran, D. K.
- Proceedings of the National Academy of Sciences, Vol. 99, Issue 12