Faculty & Research
 |
Steven B. Vik, Ph.D.ProfessorAdvisor for Undergraduate Biochemistry Majors Chair of Department of Biological Sciences 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 (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.
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.
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
