SMU Department of Biological Sciences
 
Biology Student

Faculty & Research

Steven B. Vik, Ph.D.

Professor
Advisor for Undergraduate Biochemistry Majors

Ph.D.: University of Oregon

Postdoctoral training:
Scripps Clinic and Research Foundation
Stanford University

For more information
Office: 236-DLS
Tel: 214.768.4228
Fax: 214.768.3955
Email: svik@smu.edu

Lab: 218-DLS
Tel: 214.768.2729/3896

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.

Subunit a

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 (Sazanov LA & Hinchliffe P. Science. 2006 311:1430-6). 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.

nuo Operon from E. coli

Selected Publications

(since 1998)

Vik, S.B., Patterson, A.R. and Antonio, B.J. (1998) Insertion Scanning Mutagenesis of the a Subunit of the F 1Fo ATP Synthase Near His 245 and Implications on Gating of the Proton Channel. J. Biol. Chem. 273, 16229-16234.

Long, J.C., Wang, S. and Vik, S.B. (1998) Membrane Topology of the a Subunit of the F1Fo ATP Synthase as Determined by Labeling of Unique Cysteine Residues. J. Biol. Chem. 273, 16235-16240.

Xiong, H., Zhang, D. and Vik, S.B. (1998) Subunit ε of the E. coli ATP Synthase: Novel insights into Structure and Function from Analysis of Thirteen Mutant Forms. Biochemistry 37, 16423-16429

Wada, T., Long, J.C., Zhang, D. and Vik, S.B., (1999) A Novel Labeling Approach Supports the Five-transmembrane Model of Subunit a of Escherichia coli ATP Synthase, J. Biol. Chem. 274, 17353-17357

Patterson, A.R, Wada, T. and Vik, S.B. (1999) H15 of Subunit a of the Escherichia coli ATP Synthase is Important for Assembly or Structure of the Membrane Sector Fo. Arch. Biochem. Biophys. 368, 193-197

Vik, S.B., Long, J.C., Wada,, T., Zhang, D. , (2000) A Model for the Structure of Subunit a of the Escherichia coli ATP Synthase and its Role in Proton Translocation, Biochim. Biophys. Acta, 1458, 457-466

Vik, S.B. (2000) What is the role of the epsilon subunit of the E. coli ATP synthase J. Bioenerg. Biomembr. 32, 485-491

Long, J. C., DeLeon-Rangel, J. and Vik, S. B. (2002) Characterization of the First Cytoplasmic Loop of Subunit a of the Escherichia coli ATP Synthase by Surface Labeling, Cross-linking and Mutagenesis. J. Biol Chem. 277, 27288-27293.

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. (in press 2007). Chapter 3.2.3, ATP Synthase. 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.

Vik, S. B. (in press 2007). 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.

Support

National Institutes of Health Research Grant, RO1-40508, "Structure-Function Studies of the E. coli F1Fo ATPase," 1988-2009.

Welch Foundation, 1997-2009

American Heart Association, "Quinone Binding Sites in Complex I and their possible role in disease", 2004-2006

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, ScrippsClinic 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
2000 Visiting Scientist, Universität Osuabrück, Osnabrück, Germany
 
1999-present Professor, Department of Biological Sciences, Southern Methodist University, Dallas, TX

Editorial Board

Journal of Biological Chemistry 2005-2010

Peruna