Li. Krishtalik et Wa. Cramer, ON THE PHYSICAL BASIS FOR THE CIS-POSITIVE RULE DESCRIBING PROTEIN ORIENTATION IN BIOLOGICAL-MEMBRANES, FEBS letters, 369(2-3), 1995, pp. 140-143
The topology of hydrophobic intramembrane proteins is characterized by
a statistical asymmetry in the distribution of positively-charged res
idues on the two sides of the membrane, the 'inside- or cis-positive r
ule'. A mechanism is proposed involving only neutral residue transfer.
For a tightly bound polypeptide adsorbed on the membrane and not at e
quilibrium, the pK values of the ionic residues related to dissociatio
n of the proton into the aqueous phase bulk are increased because of i
nteraction with the negative charges at the membrane surface. The pg s
hift would selectively neutralize aspartate and glutamate residues, fa
voring their translocation across the membrane, while stabilizing the
impermeant positively charged state of lysine and arginine residues.