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Trevor P. Creamer
Associate Professor of Molecular and Cellular Biochemistry
B.Sc. University of Western Australia, Australia
Ph.D. University of Western Australia, Australia
tpcrea0@uky.edu
859-323-6037
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Research Interests:
After many years of working on protein folding and related issues, the Creamer lab is now applying its expertise to the characterization of the function and conformational properties of intrinsically disordered regions (IDRs) within proteins. IDRs are regions of protein sequence that do not appear to adopt a well-defined structure. Many of these appear to gain structure (i.e. fold) when bound by another biomolecule. The folding transition that occurs upon this binding can be important for the function of the protein.
 We have chosen calmodulin (CaM) and its targets as model systems to study folding transitions within IDRs. CaM is a vital calcium sensor protein that is highly-conserved from yeast to man and is a regulator of many important enzymes. It was recently proposed that the sequences that CaM binds are often IDRs. Our current studies are focused on calcineurin (CaN), a Ser/Thr phosphotase that is activated by CaM binding. CaN plays essential roles in memory development and retention, cardiac growth, and immune system activation. It has been implicated in numerous disorders including Down syndrome, cardiac hypertrophy, and autoimmune disorders. The regulatory domain of CaN, which is a CaM substrate, is an IDR. We are investigating the CaM-CaN interaction and how this regulates CaN function.
We are planning to extend this work to include other regulators of CaN including Rcan1, a protein that plays a role in Down syndrome, and CHP1. We are also exploring folding transitions in other CaM substrates.
Representative Publications:
Creamer, TP (editor). Unfolded proteins: from denatured to intrinsically disordered. Nova Science Press, New York (2008).
Firestine AM, Chellgren VM, Rucker SJ, Lester TE, Creamer TP. Conformational properties of a peptide model for unfolded alpha-helices. Biochemistry. 2008 Mar 11;47(10):3216-24. PMID: 1826632
Stevenson B, Choy HA, Pinne M, Rotondi ML, Miller MC, Demoll E, Kraiczy P, Cooley AE, Creamer TP, Suchard MA, Brissette CA, Verma A, Haake DA. Leptospira interrogans endostatin-like outer membrane proteins bind host fibronectin, laminin and regulators of complement. PLoS ONE. 2007 Nov 14;2(11):e1188. PMID: 18000555
Chellgren BW, Miller AF, Creamer TP. Evidence for polyproline II helical structure in short polyglutamine tracts. J Mol Biol. 2006 Aug 11;361(2):362-71. PMID: 16854433
Barrett DG, Minder CM, Mian MU, Whittington SJ, Cooper WJ, Fuchs KM, Tripathy A, Waters ML, Creamer TP, Pielak GJ. Pressure perturbation calorimetry of helical peptides. Proteins. 2006 May 1;63(2):322-6. PMID: 16372358
Bhattacharyya A, Thakur AK, Chellgren VM, Thiagarajan G, Williams AD, Chellgren BW, Creamer TP, Wetzel R. Oligoproline effects on polyglutamine conformation and aggregation. J Mol Biol. 2006 Jan 20;355(3):524-35. PMID: 16321399
Chellgren BW, Creamer TP. Side-chain entropy effects on protein secondary structure formation. Proteins. 2006 Feb 1;62(2):411-20. PMID: 16315271
Whittington SJ, Chellgren BW, Hermann VM, Creamer TP. Urea promotes polyproline II helix formation: implications for protein denatured states. Biochemistry. 2005 Apr 26;44(16):6269-75. PMID: 15835915
Chellgren BW, Creamer TP. Effects of H2O and D2O on polyproline II helical structure. J Am Chem Soc. 2004 Nov 17;126(45):14734-5. PMID: 15535694
Chellgren BW, Creamer TP. Short sequences of non-proline residues can adopt the polyproline II helical conformation. Biochemistry. 2004 May 18;43(19):5864-9. PMID: 15134460
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