General Principles of Membrane Protein Folding and Stability

 

Some general principles of membrane protein structure and stability

 

Basic Principles. One broad thermodynamic principle underlies the structure and stability of membrane proteins: The thermodynamic cost of transferring charged or highly polar uncharged compounds into the oil-like hydrocarbon interior of bilayer membranes is very high. This has two consequences.

First, most of the amino acid sidechains oftransmembrane segments must be non-polar (e.g. Ala, Val, Leu, Ile, Phe).

Second, the very polar CONH groups (peptide bonds) of the polypeptide backbone of transmembrane segments must participate in hydrogen bonds (H-bonds) in order to lower the cost of transferring them into the hydrocarbon interior.

This H-bonding is most easily accomplished with alpha-helices for which all peptide bonds are H-bonded internally. It can also be accomplished with beta-sheets provided that the beta-strands form closed structures such as the beta-barrel. All membrane proteins of known three-dimensional structure adhere to these principles. Examples of the two known structural motifs, bacteriorhodopsin and a porin, are shown below.