Christine Cremo, Ph.D.
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Research Interests:
This lab is well-suited to those students and postdoctoral associates interested in a broad training in biomedical research, in modern molecular genetic techniques and in protein manipulation. Students who are interested in pursuing careers in medicine, biotechnology, or academic research will benefit from joining our dynamic collaborative team.
Our research group is interested in protein structure and function. Specifically we are interested in the structural changes that proteins undergo and how those changes are related to protein function. Our current work is focused upon molecular motor proteins. These nanomotors are in every cell of your body. They convert chemical energy into mechanical energy and thus generate force. Molecular motor proteins are responsible for the viability of almost every cell type. They are particularly important for muscles, but many non-muscle tissues, such as the brain, are loaded with motors,. Our main interest is in the function of smooth muscles. These muscles line almost every organ in the body, and also the arteries and veins. Proper function of motors is essential to maintenance of blood pressure for example, and thus are of great medical importance. We want to understand how the motors generate force and how they are controlled by cellular processes.
Many modern tools are used to extend our understanding, such as enzyme kinetics, mutagenesis, protein expression, protein crystallization, molecular modeling, mass spectroscopy, fluorescence, photo-crosslinking, electron paramagnetic resonance, organic synthesis and more. We collaborate with leading scientists worldwide with expertise in physiology, molecular biology, and physical biochemistry. Our research is funded by the National Institutes of Health and the American Heart Association.
Selected Publications:
Cremo, C. R., Herron, G. S. and Schimerlik, M. I. (1981) Solubilization of the Atrial Muscarinic Receptor: A New Detergent System and Rapid Assays, Anal. Biochem. 115, 331-338.
Cremo, C. and Schimerlik, M. I. (1983) Histrionicotoxin and Alkyl Guanidine Interactions with the Solubilized and Membrane-Bound Muscarinic Acetylcholine Receptor from Porcine Atria, Arch Biochem. Biophys. 224, 506-514.
Cremo, C. R. and Schimerlik, M. I. (1984) Photoaffinity Labeling of the Solubilized, Partially Purified Muscarinic Acetylcholine Receptor from Porcine Atria by p-Azidoatropine Methyl Iodide, Biochemistry 23, 3494.
Cremo, C. and Yount, R. G. (1987) 2’-Deoxy-3’(2’)-O-(4-Benzoyl)benzoyl, 1,N6-ethenoadenosine 5’-diphosphate, Fluorescent Photoaffinity Analogues of ADP. Synthesis, Characterization, and Interaction with Myosin Subfragment 1, Biochemistry 26, 7524-7534.
Mahmood, R., Cremo, C., Nakamaye, K. L. and Yount, R. G. (1987) The Interaction and Photolabeling of Myosin Subfragment-1 with 3’(2’)-O-(4-benzoyl)benzoyl adenosine 5’-triphosphate, J. Biol. Chem. 262, 14479-14486.
Grammer, J. C., Cremo, C. R., and Yount, R. G. (1988) UV-Induced Vanadate-Dependent Modification and Cleavage of Skeletal Myosin Subfragment 1 Heavy Chain. 1. Evidence for Active Site Modification, Biochemistry 27, 8408-8415.
Cremo, C. R. , Grammer, J. C., and Yount, R. G. (1988) UV-Induced Vanadate-Dependent Modification and Cleavage of Skeletal Myosin Subfragment 1 Heavy Chain. 2. Oxidation of Serine in the 23-kDa NH2-Terminal Tryptic Peptide, Biochemistry 27, 8415-8420.
Cremo, C. R., Grammer, J. C., and Yount, R. G. (1989) Direct Chemical Evidence that Serine-180 in the Glycine-rich Loop of Myosin Binds to ATP, J. Biol. Chem. 264, 6608-6611.
Cremo. C. R., Long, G. L. and Grammer, J. G. (1990) Photocleavage of Myosin Subfragment 1 by Vanadate, Biochemistry 29, 7982-7990.
Cremo, C. R., Neuron, J., and Yount, R. G. (1990) Interaction of Myosin Subfragment 1 with Fluorescent Ribose-Modified Nucleotides. A Comparison of Vanadate Trapping and SH1-SH2 Crosslinking, Biochemistry 29, 3309-3318.
Cremo, C. R., Grammer, J. G. and Yount, R. G. (1991) UV-induced Cleavage of Myosin by Vanadate, Methods in Enzymol. 196, 442-443.
Ko, Y. H., Cremo, C. R., and McFadden, B. A. (1992) Vanadate-Dependent Photomodification of Serine-319 and 321 in the Active Site of Isocitrate Lyase from Escherichia coli, J. Biol. Chem. 267, 91-95.
Cremo, C. R., Loo, J. A., Edmonds, C. G., & Hatlelid, K. M. (1992) Vanadate Catalyzes Photocleavage of Adenylate Kinase at Proline-17 in the Phosphate Binding Loop Biochemistry 31, 491-497.
Facemyer, K. C., & Cremo, C. R. (1992) A New Method to Specifically Label Thiophosphorylatable Proteins with Extrinsic Probes. Labeling of Serine-19 of the Regulatory Light Chain of Smooth Muscle Myosin, Bioconjugate Chemistry, 3, 408-413.
Yount, R. G., Cremo, C. R., Grammer, J. C., & Kerwin, B. C. (1992) Photochemical Mapping of the Active Site of Myosin, Phil. Trans. R. Soc. Lond. B, 336, 55-61.
Okamoto, Y., & Cremo, C. R. (1993) Photochemical Cleavage of Myosin Heavy Chain and the Effect on the Interaction with Actin, in Mechanism of Myofilament Sliding in Muscle Contraction. (Ed. H. Sugi & G. H. Pollack) Plenum Press, New York.
Facemyer, K. C., Tibeau, M. R., & Cremo, C. R. (1993) Modification of Thiophosphorylated Proteins with Extrinsic Probes, in Techniques in Protein Chemistry Vol IV, R. H. Angelletti, Ed., Academic Press, pp. 187-192.
Luo, Y., Wang, D., Cremo, C. R., Pate, E., Cooke, R., & Yount, R. G. (1995) Photoaffinity ADP Analogs a Covalently Attached Reporter Groups of the Active Site of Myosin Subfragment 1, Biochemistry, 34, 1978-1987.
Cremo, C. R. , Sellers, J. R., & Facemyer, K. C. (1995) Two Heads are Required for Phosphorylation-Dependent Regulation of Smooth Muscle Myosin, J. Biol. Chem. 270, 2171-2175.
Pouchnik, D. J., Laverman, L. E., Janiak-Spens, F., Jameson, D. M., Reinhart, G. D., & Cremo, C. R. (1996) Synthesis and Spectral Characterization of Sulfhydryl-Reactive Fluorescent Probes, Anal. Biochem. 235, 26-35.
Olney, J. J., Sellers, J. R., & Cremo, C. R. (1996) Structure and function of the 10 S conformation of smooth muscle myosin, J. Biol. Chem., 271, 20375-20384.
Gollub, J., Cremo, C. R., & Cooke, R. (1996) ADP Release Produces a Rotation of the Neck Region of Smooth Myosin but not Skeletal Myosin, Nature Structural Biology, 3, 796-802.
Grammer, J. C., Loo, J. A., Edmonds, C. G., Cremo, C. R. & Yount, R. G. (1996) Chemistry and Mechanism of Vanadate-promoted Photo-oxidative Cleavage of Myosin, Biochemistry 35, 15582-15592.
Cremo, C. R. & Geeves, M. A. (1998) Interactions of Actin and ADP with the Head Domain of Smooth Muscle Myosin: Implications for Strain-Dependent ADP Release in Smooth Muscle, Biochemistry 37, 1969-1978.
Wu, X., Clack, B., Zhi, G., Stull, J. T., and Cremo, C. R. (1999) Phosphorylation-dependent structural changes in the regulatory light chain domain of smooth muscle heavy meromyosin, J. Biol. Chem., 274, 20328-20335.
Gollub, J., Cremo, C. R., and Cooke, C. R. (1999) Phosphorylation Regulates the ADP-Induced Rotation of the Light Chain Domain of Smooth Muscle Myosin, Biochemistry 38, 10107-10118.
Ellison, P. A., Sellers, J. R. and Cremo, C. R. (2000) Kinetic properties of smooth muscle heavy meromyosin with one thiophosphorylated head , J. Biol. Chem. 275, 15142-51.
Sathyanarayanan, P.V., Cremo, C. R. and Poovaiah, B.W. (2000) Plant chimeric Ca2+/Calmodulin-dependent protein kinase. Role of the neural visinin-like domain in regulating autophosphorylation and calmodulin affinity, J. Biol. Chem., 275, 30417-22.
Cremo, C. R., Wang, F., Facemyer, K. and Sellers, J. R. (2001) Phosphorylation-dependent Regulation is Absent in a Nonmuscle Heavy Meromyosin Construct with One Complete Head and One Head Lacking the Motor Domain, J. Biol. Chem. 276, 41465-72.
Pearson, D. S., Holtermann, G., Ellison, P., Cremo, C. R. & Geeves. M. A. (2002) A novel microvolume pressure jump apparatus used for the study of nucleotide binding to muscle myosin subfragment 1, Biochem. J. 366, 643-651.
Cremo, C. R. (2003) Fluorescent Nucleotides: Synthesis and Characterization, Methods in Enzymology, 360, 128-77.
Wahlstrom, J., Randall, A., Lawson, D., Lyons, D., Seims, W., Crouch, G. J., Barr, R., Facemyer, K. C., and Cremo, C. R. (2003) Structural Model of the Regulatory Domain of Smooth Muscle Heavy Meromyosin, J. Biol. Chem. 278, 5123-5131.
Ellison, P. A., DePew, Z. S. and Cremo C. R. (2003) Both Heads of Tissue-Derived Smooth Muscle Heavy Meromyosin Bind to Actin in the Presence of ADP, J. Biol. Chem. 278. 4410-4415.
Perkins, W. J., Lorenz, R. R., Bogoger, M., Warner, D. O., Cremo, C. R., and Jones, K. A. (2003) A Novel Mechanism by which Hydrogen Peroxide Decreases Calcium Sensitivity in Airway Smooth Muscle, American Journal of Physiology, Lung Cellular and Molecular Physiology, 284(2):L324-32.
Mazhari, Sam M., Selser, Curtis T., and Cremo, Christine R. (2004) Novel sensors of the regulatory switch on the regulatory light chain of smooth muscle myosin, J. Biol. Chem. 279 (38) 39905-14.
Li, Hui-Chun, Song, Likai, Ellison, P. A., Cremo, C. R. and Fajer, P. G. (2006) Regulatory and Catalytic Domain Dynamics of Smooth Muscle Myosin Filaments, submitted to Biochemistry.