Tosteson M T, Levy J J, Caporale L H, Rosenblatt M, Tosteson D C
Department of Physiology, Harvard Medical School, Boston, Massachusetts 02115.
Biochemistry. 1987 Oct 20;26(21):6627-31. doi: 10.1021/bi00395a010.
The main component of the honey bee venom, melittin, is a cationic polypeptide containing 26 amino acids. Exposure of lipid bilayers to this peptide results in the formation of anion-selective channels with a variety of unit conductances. One of the possible causes for this heterogeneity in the conductance could be heterogeneity of the melittin preparation, and indeed, the existence of two prominent forms of naturally occurring melittin, differing only at the N-terminal amino group, has been documented. This paper describes the synthesis of the major form of melittin, using stepwise solid-phase methodology and the demonstration that the synthetic melittin, devoid of the minor component (N-formylmelittin) and other contaminants, interacts with lipid bilayers to form channels which are qualitatively indistinguishable from the ones formed by the naturally occurring toxin. This result indicates that the heterogeneity in the channels produced in bilayers by bee venom is not due to differences in the channel-forming properties of the formyl and non-formyl melittin but rather to differences in the number and orientation of melittin monomers of identical primary structure as they aggregate to form channels in the lipid bilayer.
蜜蜂毒液的主要成分蜂毒肽是一种含有26个氨基酸的阳离子多肽。脂质双层与这种肽接触会导致形成具有多种单位电导的阴离子选择性通道。电导这种异质性的一个可能原因可能是蜂毒肽制剂的异质性，实际上，已经有文献记载存在两种主要的天然蜂毒肽形式，它们仅在N端氨基处有所不同。本文描述了使用逐步固相方法合成主要形式的蜂毒肽，并证明合成的蜂毒肽不含次要成分（N-甲酰蜂毒肽）和其他污染物，它与脂质双层相互作用形成的通道在性质上与天然毒素形成的通道无法区分。这一结果表明，双层膜中由蜂毒产生的通道异质性并非由于甲酰化和非甲酰化蜂毒肽的通道形成特性不同，而是由于具有相同一级结构的蜂毒肽单体在脂质双层中聚集形成通道时数量和方向的差异。
