Faculty & Research

Steven Vik

Biological Sciences

Steven B. Vik, Ph.D.

Professor
Advisor for Undergraduate Biochemistry Majors
Chair of Department of Biological Sciences

Ph.D. University of Oregon
DLSB 236
214-768-4228

Lab: DLSB 218
Tel: 214-768-2729 or 214-768-3896

Email: svik@smu.edu


Research Interests

Protein Structure and Function/ Biochemistry of Membrane-Bound Enzymes

Dr. Vik is interested in the structure, function, and assembly of the membrane-bound enzymes that are involved in oxidative phosphorylation. His research group is currently investigating the F1F0 ATP synthase and Complex I from E. coli.

The ATP synthase is a remarkable enzyme in that it functions as a rotary motor.  During ATP synthesis electrical energy is converted to chemical energy through mechanically-driven conformational changes. The enzyme from E. coli is formed from eight different polypeptide subunits, in a stoichiometry of α3β3γδεab2c10. The subunits can be classified as rotor or stator subunits. The rotor consists of γ, ε, and the ring of c subunits.  The stator consists of α, β, δ, a, and b.  The α/β hexamer is where ATP synthesis occurs.  In the membrane, the rotor subunit c interacts with the stator subunit a.  During ATP synthesis protons enter from the periplasm, probably through subunit a.  A model for the structure of subunit a is shown below, and how it might be involved in proton translocation. More details about the interactions of subunit a with other subunits, the nature of the proton channel, and conformational changes of subunit a are currently under investigation in the lab.

Left: Subunit a has five transmembrane spanning helices. This model was determined by surface labeling of mono-cysteine mutants.

Right: Subunit a interacts with a ring of 10 c subunits to form the proton channel. Proton movement through this channel drives rotation of the gamma-epsilon complex, and subsequently ATP synthesis.

Complex I, the NADH-ubiquinone oxidore ductase in Escherichia coli is encoded by the thirteen genes of the nuo operon. It is homologous to the much larger enzyme found in mammalian mitochondrial membranes. This enzyme oxidizes NADH, reduces ubiquinone, and translocates protons across the inner membrane.  Six of the thirteen subunits (B, CD, E, F, G and I) constitute a membrane peripheral domain that includes the NADH binding site, one noncovalently bound flavin mononucleotide, and nine Fe-S centers. A high resolution structure of this segment, see below, has been determined for the enzyme from T. thermophilus (Efromov et al., Nature. 2010 465, 441-446). The other seven subunits (A, H, J, K, L, M, and N) are hydrophobic membrane proteins that are homologous to the seven proteins typically encoded by mammalian mitochondrial DNA.  These proteins are likely to be involved in proton translocation and in quinone reactions.  The three largest of the mitochondrial homologues, called L, M and N in E. coli, are related to one another. These proteins are the primary focus of the lab. A mutagenesis project is underway to dissect the structure and function of these proteins. An E. coli strain has been constructed that has the entire nuo operon (15 kb) deleted, and an expression vector containing the nuo operon has been shown to complement the deletion strain.

 

 Vik2-NADH

 

Selected Publications

(since 2003)

Zhang, D. and Vik, S.B. (2003) Helix packing in subunit a of the Escherichia coli ATP Synthase as determined by chemical labeling and proteolysis of the cysteine-substituted protein. Biochemistry 42, 331-337.

Zhang, D. and Vik, S.B. (2003) Close proximity of a cytoplasmic loop of subunit a with c subunits of the ATP synthase from Escherichia coli. J. Biol. Chem. 278, 12319-12324.

Amarneh, B. and Vik, S.B. (2003) Mutagenesis of Subunit N of the Escherichia coli Complex I. Identification of the Initiation Codon and the Sensitivity of Mutants to Decylubiquinone. Biochemistry 42, 4800-4808

DeLeon-Rangel, J., Zhang, D. and Vik, S.B. (2003) The role of transmembrane span 2 in the structure and function of subunit a of the ATP synthase from Escherichia coli. Arch. Biochem. Biophys. 418, 55-62.

Ishmukhametov, R.R., Galkin, M.A., and Vik, S.B.. (2005) Ultrafast purification and reconstitution of His-tagged cysteine-less Escherichia coli F1Fo ATP synthase. Biochim. Biophys. Acta 1706, 110-116.

Amarneh, B. and Vik, S.B. (2005) Direct Transfer of NADH From Malate Dehydrogenase to Complex I in Escherichia coli. Cell Biochem. Biophys. 42, 251-262

Vik S. B. and Ishmukhametov R. R. (2005) Structure and function of subunit a of the ATP synthase of Escherichia coli. J. Bioenerg. Biomembr. 37:445-449

Galkin M.A., Ishmukhametov R. R, and Vik S.B. (2006) A functionally inactive, cold-stabilized form of the Escherichia coli F1Fo ATP synthase. Biochim. Biophys. Acta. 1757:206-214

Amarneh B., De Leon-Rangel J., and Vik S. B. (2006) Construction of a deletion strain and expression vector for the Escherichia coli NADH:ubiquinone oxidoreductase (Complex I). Biochim. Biophys. Acta. 1757: 1557-1560

Ganti, S., and Vik S. B. (2007) Chemical modification of mono-cysteine mutants allows a more global look at conformations of the epsilon subunit of the ATP synthase from Escherichia coli. J. Bioenerg. Biomembr. 39: 99-107

Vik, S.B. (19 October 2007). Chapter 3.2.3, ATP Synthesis by Oxidative Phosphorylation. In A. Böck, R. Curtiss III, J. B. Kaper, F. C. Neidhardt, T. Nyström, K. E. Rudd, and C. L. Squires (ed.), EcoSal-Escherichia coli and Salmonella: cellular and molecular biology. [Online.] http://www.ecosal.org. ASM Press, Washington, D.C.(doi: 10.1128/ecosal.3.2.3)

Vik, S.B. (February 2008). Chapter 2, An analysis of the structure and function of Complex I from Escherichia coli. In M. I. Gonzalelz Siso (ed.), Complex I and Alternative Dehydrogenases. Transworld Research Network, Kerala, India.

Ishmukhametov, R.R., Pond, J.B., Al-Huqail, A., Galkin, M.A., and Vik, S.B. (2008) ATP synthesis without R210 of subunit a in the Escherichia coli ATP synthase. Biochim. Biophys. Acta 1777: 32-38.

Bae, L., and Vik, S.B. (2009) A more robust version of the Arginine 210-switched mutant in subunit a of the Escherichia coli ATP synthase. Biochim. Biophys. Acta 1787: 1129-1134.

Amarneh, B., and Vik, S.B. (2010) Transmembrane topology of subunit N of Complex I (NADH:Ubiquinone Oxidoreductase) from Escherichia coli. J. Bioenerg. Biomembr. 42: 511-516.

Michel, J., DeLeon-Rangel, J., Zhu, S., Van Ree, K., and Vik, S.B. (2011) Mutagenesis of the L, M, and N subunits of Complex I from Escherichia coli indicates a common role in function. PLoS One  6: e17420.

Vik, S.B. (2011) The transmembrane helices of the L, M, and N subunits of Complex I from E. coli can be assigned on the basis of conservation and hydrophobic moment analysis. FEBS Lett. 585: 1180-1184.

Li, Bo,. Vik, S. B., Tu, Y. (2012) Theaflavins inhibit the ATP synthase and the respiratory chain without increasing superoxide production. J. Nutr. Biochem. 23: 953-960.

 

Support

National Institutes of Health, Welch Foundation, American Heart Association

 

Education

  • 1975 B.S. Chemistry, California Institute of Technology
  • 1980 Ph.D. Chemistry, University of Oregon

 

Professional Experience

1980-1982 Research Associate, Department of Biochemistry, Scripps Clinic and Research Foundation, La Jolla, CA
1982-1983 Visiting Research Scholar, Chinese Academy of Sciences, Institute of Zoology, Department of Cell Biology, Beijing, People's Republic of China
1983-1987 Postdoctoral Research Fellow, Department of Biological Sciences, Stanford University, Stanford, CA
1987-1993 Assistant Professor, Department of Biological Sciences, Southern Methodist University, Dallas, TX
1993-1999 Associate Professor, Department of Biological Sciences, Southern Methodist University, Dallas, TX
1999-present Professor, Department of Biological Sciences, Southern Methodist University, Dallas, TX
2000 Visiting Scientist, Universität Osuabrück, Osnabrück, Germany
2008-2011 Visiting Professor, Department of Tea Science, Zhejiang University, Hangzhou, China
2010-2011 Chair, Department of Biological Sciences, Southern Methodist University, Dallas, TX

 

Editorial Board

Journal of Biological Chemistry 2005-2010, 2012-2017