哺乳動物的晝夜節(jié)律，是由以約24小時為周期的自我調(diào)控轉(zhuǎn)錄反饋機制掌控的,。該機制的關(guān)鍵組分是一個異二聚化轉(zhuǎn)錄活化因子,，包含兩個bHLH-PAS結(jié)構(gòu)域蛋白亞基：CLOCK和BMAL1。
5月31日Science雜志在線發(fā)表了Nian Huang等的研究論文,，以2.3埃米的分辨率解析了包含小鼠CLOCK:BMAL1 bHLH-PAS結(jié)構(gòu)域的蛋白晶體復(fù)合物的結(jié)構(gòu)生物學(xué)信息,。
該研究表明，在CLOCK和BMAL1 兩個亞基中的三個結(jié)構(gòu)域間均存在一個不同尋常的非對稱異二聚體,。bHLH,，PAS-A 和PAS-B緊密纏繞，參與二聚化相互作用,，產(chǎn)生三個不同的蛋白界面,。破壞此異二聚體界面的突變，可影響CLOCK:BMAL1復(fù)合物的穩(wěn)定性和活力,，以及晝夜節(jié)律周期性。CLOCK:BMAL1復(fù)合物結(jié)構(gòu)的解析為從原子水平理解哺乳動物晝夜節(jié)律鐘的驅(qū)動機制創(chuàng)造了良好的開端,。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
PMC:
PMID:
Crystal Structure of the Heterodimeric CLOCK:BMAL1 Transcriptional Activator Complex
Nian Huang, Yogarany Chelliah, Yongli Shan, et al.
The circadian clock in mammals is driven by an autoregulatory transcriptional feedback mechanism that takes about 24 hours to complete. A key component of this mechanism is a heterodimeric transcriptional activator consisting of two bHLH-PAS domain protein subunits, CLOCK and BMAL1. Here, we report the crystal structure of a complex containing the mouse CLOCK:BMAL1 bHLH-PAS domains at 2.3 ? resolution. The structure reveals an unusual asymmetric heterodimer with the three domains in each of the two subunits, bHLH, PAS-A and PAS-B tightly intertwined and involved in dimerization interactions, resulting in three distinct protein interfaces. Mutations that perturb the observed heterodimer interfaces affect the stability and activity of the CLOCK:BMAL1 complex as well as the periodicity of the circadian oscillator. The structure of the CLOCK:BMAL1 complex is a starting point for understanding at an atomic level the mechanism driving the mammalian circadian clock.
