Laboratory of Genetics, The Rockefeller University, New York, NY 10065, USA.
J Mol Biol. 2011 Oct 28;413(3):561-72. doi: 10.1016/j.jmb.2011.08.048. Epub 2011 Sep 3.
Period (PER) is the major transcription inhibitor in metazoan circadian clocks and lies at the center of several feedback loops that regulate gene expression. Dimerization of Drosophila PER influences nuclear translocation, repressor activity, and behavioral rhythms. The structure of a central, 346-residue PER fragment reveals two associated PAS (Per-Arnt-Sim) domains followed by a protruding α-helical extension (αF). A closed, pseudo-symmetric dimer forms from a cross handshake interaction of the N-terminal PAS domain with αF of the opposing subunit. Strikingly, a shift of αF against the PAS β-sheet generates two alternative subunit interfaces in the dimer. Taken together with a previously reported PER structure in which αF extends, these data indicate that αF unlatches to switch association of PER with itself to its partner Timeless. The variable positions of the αF helix provide snapshots of a helix dissociation mechanism that has relevance to other PAS protein systems. Conservation of PER interaction residues among a family of PAS-AB-containing transcription factors suggests that contacts mediating closed PAS-AB dimers serve a general function.
周期（PER）是真核生物生物钟的主要转录抑制剂，位于几个调节基因表达的反馈环的中心。果蝇 PER 的二聚化影响核易位、抑制活性和行为节律。一个中央的 346 残基 PER 片段的结构揭示了两个相关的 PAS（Per-Arnt-Sim）结构域，后面是一个突出的α-螺旋延伸（αF）。一个封闭的、伪对称二聚体通过 N 端 PAS 结构域与相反亚基的αF 之间的交叉握手相互作用形成。引人注目的是，αF 与 PAS β-片层的相对位置产生了二聚体中的两个替代亚基界面。与先前报道的 PER 结构中αF 延伸一起，这些数据表明，αF 松开以切换 PER 与其伴侣 Timeless 的自身关联。αF 螺旋的可变位置提供了一个螺旋解离机制的快照，该机制与其他 PAS 蛋白系统有关。包含 PAS-AB 的转录因子家族中 PER 相互作用残基的保守性表明，介导封闭 PAS-AB 二聚体的接触具有普遍功能。
