Protein and Metabolic Engineering
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Engineering of Conformational Changes in Peptides
Proteins are involved in almost every aspect of cellular function, and therefore they have evolved with a myriad of properties and capabilities. The catalytic nature of proteins is widely appreciated, and the field of Protein Engineering has emerged over the past 25 years to both study and improve the biochemical properties of proteins for a wide variety of important applications.
More recently, the physical properties and abilities of proteins and peptides have been gaining attention. For example, the hemagglutinin protein from the influenza virus undergoes a dramatic pH-triggered conformational change to promote membrane fusion during infection.
As our understanding of the natural conformational plasticity of proteins and peptides expands, these properties are increasingly being exploited for the design and engineering of new protein and peptide-based systems. For example, the well-known elastin-like peptides are known to undergo a dramatic reversible conformational change, from a disordered peptide to a collapsed b-spiral with reduced solubility, in response to changes in temperature, pH, or ionic strength. This transition has been termed the inverse temperature transition, due to the fact that the peptides become more ordered (not less) with increased temperature, and this effect has been extensively characterized. The elastin-like peptide conformational change has been used as a building-block for a variety of rationally engineered systems, including advanced bioseparations, environmental remediation, drug delivery, molecular switches, tissue engineering, and bionanotechnology.
We are developing a new methods for the Directed Evolution of peptides that exhibit novel conformational behavior in response to environmental stimuli. We are developing new sensing systems that can be used to report the conformational behavior of an attached peptide. One approach is to use a single chain antibody fragment (scFv) that has a variable binding affinity depending on the conformational state of its linker peptide. The new peptides that can be discovered using these creative approaches will be extensively characterized, which will to help to further elucidate the molecular underpinnings of the conformational behavior of peptides. And, the new peptides will be immediately valuable for use in many avenues of research including biotechnology, synthetic biology, nanotechnology, biosensing and drug discovery.
- Banta S, Wheeldon IR, and Blenner M. Protein engineering in the development of functional hydrogels. Annu Rev Biomed Eng. 2010 Aug 15;12:167-86. DOI:10.1146/annurev-bioeng-070909-105334 |
- Chockalingam K, Lu HD, and Banta S. Development of a bacteriophage-based system for the selection of structured peptides. Anal Biochem. 2009 May 1;388(1):122-7. DOI:10.1016/j.ab.2009.01.042 |
- Casali M, Banta S, Zambonelli C, Megeed Z, and Yarmush ML. Site-directed mutagenesis of the hinge peptide from the hemagglutinin protein: enhancement of the pH-responsive conformational change. Protein Eng Des Sel. 2008 Jun;21(6):395-404. DOI:10.1093/protein/gzn018 |
- Blenner MA and Banta S. Characterization of the 4D5Flu single-chain antibody with a stimulus-responsive elastin-like peptide linker: a potential reporter of peptide linker conformation. Protein Sci. 2008 Mar;17(3):527-36. DOI:10.1110/ps.073257308 |
- Chockalingam K, Blenner M, and Banta S. Design and application of stimulus-responsive peptide systems. Protein Eng Des Sel. 2007 Apr;20(4):155-61. DOI:10.1093/protein/gzm008 |
- Banta S, Megeed Z, Casali M, Rege K, and Yarmush ML. Engineering protein and peptide building blocks for nanotechnology. J Nanosci Nanotechnol. 2007 Feb;7(2):387-401.