Internal packing of helical membrane proteins

Helix packing is important in the folding, stability, and association of me mbrane proteins, Packing analysis of the helical portions of 7 integral mem brane proteins and 37 soluble proteins show that the helices in membrane pr oteins have higher packing values (0.431) than in soluble proteins (0.405), The highest packing values in integral membrane proteins originate from sm all hydrophobic (G and A) and small hydroxyl-containing (S and T) amino aci ds, whereas in soluble proteins large hydrophobic and aromatic residues hav e the highest packing values, The highest packing values for membrane prote ins are found in the transmembrane helix-helix interfaces. Glycine and alan ine have the highest occurrence among the buried amino acids in membrane pr oteins, whereas leucine and alanine are the most common buried residue in s oluble proteins, These observations are consistent with a shorter axial sep aration between helices in membrane proteins. The tight helix packing revea led in this analysis contributes to membrane protein stability and likely c ompensates for the lack of the hydrophobic effect as a driving force for he lix-helix association in membranes.