Tompa P, Tusnády G E, Cserzo M, Simon I
Institute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, P.O. Box 7, H-1518 Budapest, Hungary.
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4431-6. doi: 10.1073/pnas.071308398. Epub 2001 Apr 3.
The prion protein displays a unique structural ambiguity in that it can adopt multiple stable conformations under physiological conditions. In our view, this puzzling feature resulted from a sudden environmental change in evolution when the prion, previously an integral membrane protein, got expelled into the extracellular space. Analysis of known vertebrate prions unveils a primordial transmembrane protein encrypted in their sequence, underlying this relocalization hypothesis. Apparently, the time elapsed since this event was insufficient to create a "minimally frustrated" sequence in the new milieu, probably due to the functional constraints set by the importance of the very flexibility that was created in the relocalization. This scenario may explain why, in a structural sense, the prion protein is still en route toward becoming a foldable globular protein.
朊病毒蛋白在生理条件下能够呈现多种稳定构象，显示出独特的结构模糊性。我们认为，这一令人困惑的特征源于进化过程中的一次突然环境变化，当时朊病毒（以前是一种整合膜蛋白）被排到细胞外空间。对已知脊椎动物朊病毒的分析揭示了其序列中编码的一种原始跨膜蛋白，这支持了这种重新定位假说。显然，自该事件发生以来经过的时间不足以在新环境中产生一个“最小受挫”序列，这可能是由于重新定位过程中产生的灵活性的重要性所设定的功能限制。这种情况可能解释了为什么从结构意义上讲，朊病毒蛋白仍在朝着成为可折叠球状蛋白的方向发展。
