Providence L L, Andersen O S, Greathouse D V, Koeppe R E, Bittman R
Department of Physiology and Biophysics, Cornell University Medical College, New York, New York 10021, USA.
Biochemistry. 1995 Dec 19;34(50):16404-11. doi: 10.1021/bi00050a022.
Chiral interactions are often important determinants for molecular recognition in chemistry and biochemistry. In order to determine whether the phospholipid backbone could be important for the conformational preference of membrane-spanning channels, we made use of the linear pentadecapeptide antibiotic gramicidin A (gA+) and a Trp-->Phe-substituted gA+ analogue, gramicidin M+ (gM+), as well as their enantiomers [gramicidin A- (gA-) and gramicidin M- (gM-), respectively]. All four analogues form conducting channels in planar bilayers formed from the dialkylphospholipids (R)- or (S)- dioleylphosphatidylcholine or from the diacylphospholipid (R)-dioleoylphosphatidylcholine. The characteristics of channels formed by the two gramicidin A enantiomers, or the two gramicidin M enantiomers, in membranes formed by either of the dioleylphosphatidylcholine enantiomers are indistinguishable. Similarly, channels formed by either pair of gramicidin enantiomers in dioleoylphosphatidylcholine bilayers are indistinguishable. We conclude that chiral interactions between gramicidin channels and the lipids in the host bilayer cannot be important determinants of gramicidin channel structure or function. The membrane/solution interface, therefore, seems to organize the channel structure because of the general characteristics of the nonpolar/polar transition at the interface rather than because of specific chemical interactions.
手性相互作用通常是化学和生物化学中分子识别的重要决定因素。为了确定磷脂主链对于跨膜通道的构象偏好是否重要，我们使用了线性十五肽抗生素短杆菌肽A（gA+）和色氨酸被苯丙氨酸取代的gA+类似物短杆菌肽M+（gM+），以及它们的对映体[分别为短杆菌肽A-（gA-）和短杆菌肽M-（gM-）]。所有这四种类似物在由二烷基磷脂（R）-或（S）-二油酰磷脂酰胆碱或由二酰基磷脂（R）-二油酰磷脂酰胆碱形成的平面双层中形成导电通道。由两种短杆菌肽A对映体或两种短杆菌肽M对映体在由任何一种二油酰磷脂酰胆碱对映体形成的膜中形成的通道的特征是无法区分的。同样，由任何一对短杆菌肽对映体在二油酰磷脂酰胆碱双层中形成的通道也是无法区分的。我们得出结论，短杆菌肽通道与主体双层中的脂质之间的手性相互作用不可能是短杆菌肽通道结构或功能的重要决定因素。因此，膜/溶液界面似乎是由于界面处非极性/极性转变的一般特征而不是由于特定的化学相互作用来组织通道结构。
