Faculty & Research
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Steven B. Vik, Ph.D.ProfessorAdvisor for Undergraduate Biochemistry Majors Ph.D.: University of Oregon Postdoctoral training: |
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.
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.
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
