Protein Folding

Important Terms (Protein Folding)

Absorbance spectroscopy Monitors conformational transitions in macromolecules by measuring absorbance changes, usually in the aromatic region of the ultraviolet (UV) spectrum. Circular dichroism A very commonly used method for studying protein conformational changes. Fluorescence The most sensitive of the commonly used optical methods for studying protein unfolding transitions. Nuclear magnetic resonance A powerful method for […]

Protein Folding

PROTEINS are only functional as enzymes, transport agents, receptors, and so forth when they exist in a folded, three-dimensional, native structure. The means by which this folded structure is achieved remains one of the most important questions in biochemistry and molecular biology. Current efforts toward sequencing the human genome and the genomes of other organisms […]

INTRODUCTION (Protein Folding)

We have interest in protein structure and function at both a fundamental and a practical level. There is astounding beauty in the mastery with which nature has tailored molecules for specific functions, activity levels, regulatory properties, and integration into complex macromolec-ular assemblies. As will be discussed, in most cases, these molecules assume a final stably […]

STABILITY OF THE TERTIARY FOLD (Protein Folding)

Stability of a protein is usually studied by observing the energetics of unfolding transitions given by the equations below: These equations apply to a simple two-state transition between the native (N) and the unfolded (U) state given by the equilibrium constant Kun. This is, by definition, a cooperative process without a detectable intermediate species. The […]

FOLDING PATHWAYS

The intramolecular interactions discussed above stabilize the final folded structure of a protein. However, knowledge of the end states, N and U, tells us nothing of the path taken between them. Proteins fold on the time scale of microseconds to hundreds of seconds. It is impossible to sample all possible conformations during this time and […]

EMPIRICAL APPROACHES (Protein Folding)

A. General Experimental Strategies As discussed above, experimental studies of protein folding reactions fall into the category of either equilibrium or kinetics studies, with the former yielding thermodynamic information about the energy differences between the native and denatured structural states and the latter studies providing information about the folding pathway and the height of energy […]

CLOSING COMMENTS (Protein Folding)

The empirical approaches mentioned above have afforded great insight into the transition from a linear sequence of amino acids into a final tertiary structure. Researchers in the field continue to pioneer new techniques that give insight into the complex inter- and intramolecular interactions that dictate structure and function of proteins. These efforts coupled with computational […]