Koeppe R E, Anderson O S
Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville 72701, USA.
Annu Rev Biophys Biomol Struct. 1996;25:231-58. doi: 10.1146/annurev.bb.25.060196.001311.
The chemical design or redesign of proteins with significant biological activity presents formidable challenges. Ion channels offer advantages for such design studies because one can examine the function of single molecular entities in real time. Gramicidin channels are attractive for study because of their known structure and exceptionally well-defined function. This article focuses on amino acid sequence changes that redesign the structure or function of gramicidin channels. New, and functional, folded states have been achieved. In some cases, a single amino acid sequence can give rise to several (up to three) functional conformations. Single amino acid substitutions confer voltage-dependent channel gating. The findings provide insight into the folding of integral membrane proteins, the importance of tryptophan residues at the membrane/water interface, and the mechanism of channel gating.
对具有显著生物活性的蛋白质进行化学设计或重新设计面临着巨大挑战。离子通道为这类设计研究提供了优势，因为可以实时检测单个分子实体的功能。短杆菌肽通道因其已知结构和极为明确的功能而成为有吸引力的研究对象。本文聚焦于能重新设计短杆菌肽通道结构或功能的氨基酸序列变化。已经实现了新的功能性折叠状态。在某些情况下，单一氨基酸序列可产生几种（多达三种）功能构象。单个氨基酸取代赋予通道电压依赖性门控特性。这些发现为深入了解整合膜蛋白的折叠、膜/水界面处色氨酸残基的重要性以及通道门控机制提供了线索。
