ULTIMATE COMPUTING - Quantum Consciousness Studies

Protein Conformational Dynamics 135
percent of all mammalian cell proteins undergo phosphorylation as a regulatory or
programming mechanism (Alberts et al., 1983).
The laws of thermodynamics demand that free energy be depleted when work
is performed. Therefore, protein molecules cannot show net movement (as do
microtubules and other cytoskeletal proteins) without some added source of
energy. Phosphorylation is one way by making one step irreversible. Another is to
drive allosteric changes by the hydrolysis of an ATP molecule, converting it to
ADP (or hydrolyzing GTP to GDP). The energy released in the hydrolysis
reaction is imparted to the protein, pushing it to a higher energy state. The precise
mechanism by which this energy is utilized and transferred by proteins is
unknown.
Besides generating mechanical force, allosteric proteins can use the energy of
ATP phosphorylation and hydrolysis to do other forms of work, such as pumping
specific ions into or out of the cell. An allosteric protein known as “sodium
potassium ATPase” which is found in the membrane of all animal cells including
nerve cells, pumps three sodium ions out of the cell and two potassium ions in
during each cycle of conformational change driven by ATP mediated
phosphorylation. This ATP driven pump creates ion gradients across the cell
membrane. The energy stored in ion gradients is harnessed by conformational
changes in other membrane proteins: ion channels. When these are triggered to
open in nerve membranes, a conformational change initiated by a voltage change,
ligand binding, or allosteric effect from membrane or cytoskeletal protein permits
ions to passively diffuse. The passage of charged ions depolarizes the membrane
as part of a local gated potential or traveling action potential.
The ion flow may also drive other membrane bound protein pumps that
transport glucose or amino acids into the cell. Energy available in
proton/hydrogen ion gradients across the inner mitochondrial membranes is used
to synthesize most of the ATP used in the animal world. Actin and myosin and
other proteins create contractile force in muscle by cooperative conformational
changes induced by ATP hydrolysis. Within bending cilia, contractile protein
bridges which span between microtubules hydrolyze ATP to drive their
mechanical activities. ATP and other energy producing molecules are the fuel of
biological protein engines. Less well understood, however, is their control,
guidance and orchestration.
6.4 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