Structural Biochemistry/Membrane Proteins/Organizational Scheme for Protein Function

There are three factors that contribute to the function of membrane proteins: structure, dynamics, and environment. These three work in correlation with each other in order to determine the unique function, as seen from the figure below.

Structure

Oligomerization is when a small peptides (i.e. monomer, dimer, trimer) are added to the protein. This affects the structure and therefore changes the function. There are four main explanations for this:

1. Functional Role

Most likely came about from evolution

Ex) Cytochrome b₆f dimer forms an electron transfer bridge

Rhodopsin dimerization regulates G-protein coupling

2. Selecting Stabilizing Mutants

3. Increase Genetic Efficiency

Code for a single unit to form a larger structure

4. Dense Packing

Optimizes functional output and eliminates unfavorable protein interactions

Strongly bound lipids and specific site receptors for water molecules gives rise to structural and functional variability. This means that the structure is stabilized and the functionality of the membrane protein is increased. For example:

In cytochrome b₆f, the lipids act as stabilizers or functional restraints

In the ATP/ADP carrier, activity is decreased with the removal of the ligands.

Dynamics

In short, dynamics is important because it regulates how much energy is spent relative to how much work is done. One model of dynamics in membrane proteins is the Induced Transition Fit Mechanism. In this mechanism, the metabolite binds only at the highest energy states, despite there being many different conformations.

$\Delta G_{A\rightarrow B}=\sum _{i=1}^{N-1}\Delta G_{i\rightarrow i+1}$

This equation is the total free energy, also known as Gibbs Free Energy. The equation mathematically expresses the sum of all the intermediate(transition) states. The overview of dynamics of membrane protein is depending on which state the metabolite chooses will determine the amount of work that is need, which will determine the protein efficiency and the function.

Environment

Environment is an important factor in understanding the function of the membrane protein. In studying the structure of the membrane protein, it is isolated from the rest of the membrane components. However, in order to get the holistic view of the membrane protein, the environment in which it lives should be examined. The reality of how the protein interacts with the other components of the cell is important in understanding the function. The path in which the protein takes can be altered by the physical constraints set by the environment. Physical properties affect the efficiency of the membrane protein. Several examples that affect the structure and function are: lateral tension, hydrophobic matching, electrostatics, and curvature elastic stress. By changing these properties, the cell can fine-tune it's function.

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References:

Sachs, Jonathan N., and Donald M. Engelman. "Introduction to the Membrane Protein Reviews: The Interplay of Structure, Dynamics, and Environment in Membrane Protein Function." Annual Review of Biochemistry 75 (2006): 707-12. Print.