Protein Cooperativity Historical View

An interesting idea regarding the control of protein conformational state and utilization of energy was proposed by Szent-Gyorgyi (1948). He suggested that proteins behave as semiconductors and that electrons "hop" between specific intraprotein regions. Experimental data, however, showed that the intraprotein energy band gap was too great to support such a concept. Utilization of dynamic biological and protein conformational energy remained enigmatic through the 1950's and 1960's.

A focal point in the history of attempts to understand protein conformational dynamics was a 1973 meeting of the New York Academy of Science (which also hosted a landmark meeting concerning microtubules in the same year). The twin mysteries of how ATP energy was utilized to produce mechanical protein events, and how energy and information were transferred in proteins and organelles were addressed by a gallery of scientists. The prevalent theme was "a crisis in bioenergetics," in that cooperative processes of obvious importance in biological systems were unexplained. One idea which generated controversy was that electromagnetic resonance energy was transferred between periodically arrayed excitation sites. At that meeting, C. W. F. McClare (1974) proposed that ATP

induced excited states ("excitons") were coupled by infrared dipoles in protein biostructures to provide a communicative medium. McClare concluded:

there is yet another level of organization in biological systems: a tuned resonance between energy levels in different molecules that enables bioenergetic machines to operate rapidly and yet efficiently.

This concept was supported by several allies including Wei (1974) who suggested dipole coupling among membrane proteins to explain nerve functions. McClare's general model of resonant dipole coupling was greeted by skepticism, however. Highly respected biochemist Gregorio Weber (1974) raised two objections. He noted that at least some of the emitted energy following molecular excitation is emitted in 10-12 seconds, too short to be utilized by biomolecules. The second objection referred to the transfer of quantum vibrational energy through the surrounding medium. The process of dipole-dipole coupling involves a similarity of the energies emitted and received, and requires that the interacting oscillators be surrounded by a medium transparent to the wavelength of the transferred energy quantum. Water surrounds every biomolecule and provides a medium which appeared to be opaque to the infrared energy McClare described. Weber implied any emitted energy would be dissipated as heat to the water environment. McClare countered, unconvincingly, that systems could have evolved to be able to slow down the relaxation and energy emission, and that such systems may be somehow separated from the aqueous phase. A consensus was that energy needed to be stored for a nanosecond or longer to be useful.

The mode of energy and information transfer was described in other comparable ways by different scientists. Several considered propagating packages of conformational or acoustic energy: "phonons." A phonon can be defined as a propagated lattice vibration, an intranuclear vibration of a carbon-nitrogen bond that propagates in a protein lattice. The transmission of phonons occurs at the speed of sound, so they are not resonance transfer phenomena but a propagated vibration in a periodic lattice. In 1967 Straub postulated that protein lattices contain phonons which must be isolated from their aqueous environment. At the New York Academy meeting in 1973 he suggested that hydrophobic interactions like Van der Waals forces could contain phonons in the lattice and shield them from the aqueous bath. The concept of "conformon," a quantum of protein conformational energy coupled to discrete protein states was independently described by Green (1970) and Ji (1974) in America, and Volkenstein (1972) in the Soviet Union. Later, A. S. Davydov of the Soviet Union proposed that mechanical conformational movements in proteins were nonlinearly coupled to electronic bond distortion or charge movement, resulting in propagating waves called "solitons." These models all faced a common problem of shielding from the aqueous environment. One possible resolution of this problem is that the water surrounding proteins may be "ordered" and resonantly coupled rather than thermally dissipating protein excitation energy. Another is that hydrophobic interactions exclude water from areas where important bioenergetic interactions occur.

0 0

Post a comment