Introduction to the TRP Cage Problem Space

Pedagogy

A unique tool to enable students to discuss and research problems posed in the context of protein structure and function, using Trpcage, a 20 residue polypeptide that is one of the smallest model proteins synthesized to date:

Basics

What defines a protein?

Discussion in terms of stable folding.

Protein Sequence --> Structure

What is the role of secondary and tertiary structure?

A discussion of thermodynamic stability and entropy-driven folding due to the hydrophobic effect.

Why is the Trpcage motif so effective in inducing folding?

Specific residues which are important.

Molecular Biology, Genomics/Proteomics, Pharmacology:

• Based on homology search for this motif in larger proteins--Evolution, conservation, function.
• GLP-I receptor site and control of diabetes.
• Exendin-4 (Gila Monster Lizard Saliva) and Glucagon-Like-Peptide I (GLP-I) as drugs for diabetes.
• Model binding to the GLP-1 receptor using a ‘homologous” receptor crystal structure, such as Methuselah, a G membrane protein-coupled receptor [GPCR]? Does it work? Do other homologous receptors exist? Do they work? Compare binding of Exendin-4, GLP-1, and a “truncated” Exendin-4 (Trp Cage).
• The crucial role of GPCR family proteins as key transducers of biological signals

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