痘病毒（如天花）通過產(chǎn)生一種被稱為K3L的蛋白來破壞宿主防衛(wèi)系統(tǒng),。該蛋白能夠非常像地模仿“蛋白激酶R”（PKR）的基質(zhì)，后者是脊椎動物先天免疫系統(tǒng)的一個重要組成部分,。Elde等人發(fā)現(xiàn)，PKR是在靈長類引人注目的積極選擇過程中,、通過在K3L 和 PKR相遇處替換氨基酸形成的,。這些演化性變化增加了宿主挫敗模仿的機會，其中兩個對手在進行一場分子“軍備競賽” ,，試圖通過斗智斗勇戰(zhàn)勝對方,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 457, 485-489 (22 January 2009) | doi:10.1038/nature07529
Protein kinase R reveals an evolutionary model for defeating viral mimicry
Nels C. Elde1, Stephanie J. Child2, Adam P. Geballe2,3,4 & Harmit S. Malik1
1 Division of Basic Sciences,
2 Division of Human Biology, and,
3 Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
4 Departments of Medicine and Microbiology, University of Washington, Seattle, Washington 98115, USA
Distinguishing self from non-self is a fundamental biological challenge. Many pathogens exploit the challenge of self discrimination by employing mimicry to subvert key cellular processes including the cell cycle, apoptosis and cytoskeletal dynamics1, 2, 3, 4, 5. Other mimics interfere with immunity6, 7. Poxviruses encode K3L, a mimic of eIF2α, which is the substrate of protein kinase R (PKR), an important component of innate immunity in vertebrates8, 9. The PKR–K3L interaction exemplifies the conundrum imposed by viral mimicry. To be effective, PKR must recognize a conserved substrate (eIF2α) while avoiding rapidly evolving substrate mimics such as K3L. Using the PKR–K3L system and a combination of phylogenetic and functional analyses, we uncover evolutionary strategies by which host proteins can overcome mimicry. We find that PKR has evolved under intense episodes of positive selection in primates. The ability of PKR to evade viral mimics is partly due to positive selection at sites most intimately involved in eIF2α recognition. We also find that adaptive changes on multiple surfaces of PKR produce combinations of substitutions that increase the odds of defeating mimicry. Thus, although it can seem that pathogens gain insurmountable advantages by mimicking cellular components, host factors such as PKR can compete in molecular 'arms races' with mimics because of evolutionary flexibility at protein interaction interfaces challenged by mimicry.
