Fleishman Sarel J, Unger Vinzenz M, Ben-Tal Nir
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv 69978, Israel.
Trends Biochem Sci. 2006 Feb;31(2):106-13. doi: 10.1016/j.tibs.2005.12.005. Epub 2006 Jan 10.
Transmembrane (TM) proteins constitute 15-30% of the genome, but <1% of the structures in the Protein Data Bank. This discrepancy is disturbing, and emphasizes that structure determination of TM proteins remains challenging. The challenge is greatest for proteins from eukaryotes, the structures of which remain intractable despite tremendous advances that have been made towards structure determination of bacterial TM proteins. Notably, >50% of the membrane protein families in eukaryotes lack bacterial homologs. Therefore, it is conceivable that many more years will elapse before high-resolution structures of eukaryotic TM proteins emerge. Until then, integrated approaches that combine biochemical and computational analyses with low-resolution structures are likely to have increasingly important roles in providing frameworks for the mechanistic understanding of membrane-protein structure and function.
跨膜（TM）蛋白占基因组的15%-30%，但在蛋白质数据库中的结构却不到1%。这种差异令人不安，凸显出跨膜蛋白的结构测定仍然具有挑战性。对于真核生物的蛋白质来说，挑战最为严峻，尽管在细菌跨膜蛋白的结构测定方面已经取得了巨大进展，但真核生物跨膜蛋白的结构仍然难以确定。值得注意的是，真核生物中超过50%的膜蛋白家族缺乏细菌同源物。因此，可以想象，在真核生物跨膜蛋白的高分辨率结构出现之前，还需要很多年的时间。在此之前，将生化和计算分析与低分辨率结构相结合的综合方法，可能会在为膜蛋白结构和功能的机制理解提供框架方面发挥越来越重要的作用。
