細胞功能依賴于錯綜復雜的信號作用網(wǎng)絡,，這些網(wǎng)絡包含多個蛋白信號作用核心,，它們與幾個合作伙伴發(fā)生相互作用,，來調(diào)控多個下游信號。對這樣一個核心（即腺病毒“早期區(qū)域1A” (E1A) 致癌蛋白）所做的這項研究,，利用新穎的單分子FRET測定來克服整合問題,，直接探測E1A與兩個關(guān)鍵合作伙伴的變構(gòu)相互作用。這些結(jié)果顯示了一個引人注目的合作性調(diào)制方式,，它是由多種相互作用及E1A相互作用主題（interaction motifs）的有無調(diào)控的,。
變構(gòu)相互作用的這樣一種調(diào)制方式，可能是內(nèi)在紊亂的核心蛋白（hub proteins）的一個共同特征,。（生物谷Bioon.com）
生物谷推薦英文摘要:
Nature doi:10.1038/nature12294
Modulation of allostery by protein intrinsic disorder
Allan Chris M. Ferreon,Josephine C. Ferreon,Peter E. Wright & Ashok A. Deniz
Allostery is an intrinsic property of many globular proteins and enzymes that is indispensable for cellular regulatory and feedback mechanisms. Recent theoretical and empirical observations indicate that allostery is also manifest in intrinsically disordered proteins, which account for a substantial proportion of the proteome . Many intrinsically disordered proteins are promiscuous binders that interact with multiple partners and frequently function as molecular hubs in protein interaction networks. The adenovirus early region 1A (E1A) oncoprotein is a prime example of a molecular hub intrinsically disordered protein. E1A can induce marked epigenetic reprogramming of the cell within hours after infection, through interactions with a diverse set of partners that include key host regulators such as the general transcriptional coactivator CREB binding protein (CBP), its paralogue p300, and the retinoblastoma protein (pRb; also called RB1). Little is known about the allosteric effects at play in E1A–CBP–pRb interactions, or more generally in hub intrinsically disordered protein interaction networks. Here we used single-molecule fluorescence resonance energy transfer (smFRET) to study coupled binding and folding processes in the ternary E1A system. The low concentrations used in these high-sensitivity experiments proved to be essential for these studies, which are challenging owing to a combination of E1A aggregation propensity and high-affinity binding interactions. Our data revealed that E1A–CBP–pRb interactions have either positive or negative cooperativity, depending on the available E1A interaction sites. This striking cooperativity switch enables fine-tuning of the thermodynamic accessibility of the ternary versus binary E1A complexes, and may permit a context-specific tuning of associated downstream signalling outputs. Such a modulation of allosteric interactions is probably a common mechanism in molecular hub intrinsically disordered protein function.
