Faculty & Research
 |
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 (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 (online 21 Mar 2011)
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 |
| 2008-2010 | Visiting Professor, Department of Tea Science, Zhejiang University, Hangzhou, China |
Editorial Board
Journal of Biological Chemistry 2005-2010
