GRAMICIDIN CHANNEL FUNCTION DOES NOT DEPEND ON PHOSPHOLIPID CHIRALITY

Chiral interactions are often important determinants for molecular rec ognition in chemistry and biochemistry. In order to determine whether the phospholipid backbone could be important for the conformational pr eference of membrane-spanning channels, we made use of the linear pent adecapeptide antibiotic gramicidin A (gA(+)) and a Trp --> Phe-substit uted gA(+) analogue, gramicidin M(+) (gM(+)), as well as their enantio mers [gramicidin A(-) (gA(-)) and gramicidin M(-) (gM(-)), respectivel y]. All four analogues form conducting channels in planar bilayers for med from the dialkylphospholipids (R)- or (S)-dioleylphosphatidylcholi ne or from the diacylphospholipid (R)-dioleoylphosphatidylcholine. The characteristics of channels formed by the two gramicidin A enantiomer s, or the two gramicidin M enantiomers, in membranes formed by either of the dioleylphosphatidylcholine enantiomers are indistinguishable. S imilarly, channels formed by either pair of gramicidin enantiomers in dioleylphosphatidylcholine bilayers are indistinguishable. We conclude that chiral interactions between gramicidin channels and the lipids i n the host bilayer cannot be important determinants of gramicidin chan nel structure or function. The membrane/solution interface, therefore, seems to organize the channel structure because of the general charac teristics of the nonpolar/polar transition at the interface rather tha n because of specific chemical interactions.