HLA-A*2402多肽复合物的两种构象——对Wolynes理论的补充

Two conformations of pHLA-A*2402: a supplement to Wolynes’ theory

摘要:

Wolynes曾经提出，蛋白质的折叠沿着能量降低的方向进行，当达到一个能量的局部最低点，蛋白质就达到了一个相对稳定的状态。有些能量的局部最低点并非生物所需要，这样的能量最低点就成了能量陷阱。Wolynes的能量通道理论和自然选择学说很好地解释了蛋白质在生理状态下的高效折叠，而非掉入能量陷阱。至于存不存在可以逃脱自然选择的能量陷阱，一直没有明确的答案。文章发现HLA-A*2402多肽复合物(pHLA-A*2402)复性后至少存在两种不同的构象，并通过对其与TCR及CD8αα相互作用的研究，发现在pHLA-A*2402中存在两个可以逃脱自然选择的能量陷阱。

Abstract:

Wolynes argued that the track of a protein’s folding was directed by the tendency of lowering its energy, and thus when a local minimum of its energy was reached, a relatively stable conformation was formed. However not all of the local minimums will lead the protein to a biologically useful conformation, for those otherwise are called energy traps. Wolynes energy landscape theory and natural selection have well explained the high efficiency of protein folding in vivo, instead of being stuck in energy traps. As to whether a protein can assume different conformations with the same bioactivity, there is no clear answer yet. In this paper, two conformational states of a pHLA-A*2402 are discovered after refolding, and by studying their interactions with TCR and CD8αα, two conformations of pHLA-A*2402 are confirmed of having escaped from natural selection.