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Trevor P. Creamer Click here to enter the Creamer Lab Research Interests | Publications | PubMedThe main interests of this laboratory are protein structure and function. We are studying both protein structure and interactions between proteins. We accomplish this using a variety of computational and experimental methods. The specific questions we are currently tackling include: 1) what are the physical determinants of secondary structure in peptides and proteins and how do these relate to interactions between proteins, and 2) what are structures and functions are associated with low-complexity protein sequences ? We are also continuing our long-standing studies of aspects of the protein-folding problem. All of this research can be characterized as ... Structural Bioinformatics and Experimental Studies of Protein Structure and Function.Proteins are the cellular machinery. The vast majority of biological processes in cells are controlled and/or performed by proteins. Often this involves proteins interacting with one another. These interactions are usually very specific: a given protein might interact only with one or two other specific proteins. How these proteins recognize each other in the crowded cell environment and how they physically interact with one another are of great interest. We are particularly interested in proline-rich regions of sequence (PRR's) that act as protein-protein interaction domains. Such sequences, which are generally >30% proline in content, are known to interact with small, modular protein domains such as SH3, WW and WVH1 domains. They are involved in numerous vital processes such as cell motility, signal transduction, transcription and the immune system.
Notably the PPII conformation is also adopted by sequences devoid of proline. There is currently great interest in the role this structure plays in the protein folding process. In particular, it was hypothesized some thirty years ago that protein unfolded states possess a great deal of PPII character. This hypothesis has been mostly ignored until recently. My laboratory has been at the forefront in recent efforts to determine whether unfolded protein states really do possess significant PPII character. Low-complexity sequences are protein sequences that are highly enriched in one or a handful of residues types. PRR's are low-complexity sequences enriched in proline. These are surprisingly common - to the point that we feel they must, at least sometimes, be playing important functional roles. Very little is known about the functional roles, or structural tendencies of these sequences. We are examining the occurrence of low-complexity sequences in fully-sequenced genomes, and are embarking on studies of their conformational properties (our work on PRR's is an initial step).
K.L. Sim and T.P. Creamer. Abundance and distributions of Eukaryote protein simple sequences. Molecular and Cellular Proteomics 1:983-99 (2002). T.P. Creamer and M.N. Campbell. Determinants of the polyproline II helix from modeling studies. Advances in Protein Chemistry 62:263-282 (2002). A.L. Rucker and T.P. Creamer. Polyproline II helical structure in protein unfolded states: Lysine peptides revisited. Protein Science 11:980-985 (2002). M.A. Kelly, B.W. Chellgren, A.L. Rucker, J.M. Rucker, M.G. Fried, A.-F. Miller and T.P. Creamer. Host-guest study of left-handed polyproline II helix formation. Biochemistry 40:14376-14383 (2001). T.P. Creamer. Side-chain conformational entropy in protein unfolded states. Proteins 40:443-450 (2000). B.J. Stapley and T.P. Creamer. A survey of left-handed polyproline II helices. Protein Science 8:587-595 (1999). T.P. Creamer. Left-handed polyproline II helix formation is (very) locally driven. Proteins 33:218-226 (1998).
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PRR's
are often assumed to adopt the left-handed polyproline II (PPII) helical
conformation. This is the same conformation as adopted by a single strand of
collagen. We are elucidating the physical determinants of PPII helix formation
using both computational and experimental methods. Computational methods include
computer simulations, conformational searches and surveys of known structures.
Our main experimental tools are circular dichroism (CD) and NMR spectroscopy.
