Functional and Structural Analyses of Cryptochrome
Functional and Structural Analyses of Cryptochrome
复制标题
隐花色素的功能和结构分析
DOI：
--
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发表时间：
2003
影响因子：
4.8
通讯作者：
T. Todo
中科院分区：
文献类型：
--
作者：
J. Hirayama;Haruki Nakamura;T. Ishikawa;Yuri Kobayashi;T. Todo
小鼠mCRY1和斑马鱼zCRY1a和zCRY3属于DNA光解酶/隐色素家族。MCRY1和zCRY1a抑制时钟：BMal1介导的转录，而zCRY3不抑制。建立了zCRY1a和zCRY3之间的相互嵌合体，以确定负责核转位的zCRY1a区域、与CLOCK：BMal1异源二聚体的相互作用以及CLOCK：BMal1介导的转录抑制。共鉴定出3个区域：RD-2a-(126-196)、RD-1-(197-263)和RD-2b-(264-293)。该家族的蛋白质由N-端的α/β结构域和C-端的螺旋结构域组成，通过结构域间环连接。RD-2a位于该环内，RD-1位于N端50个氨基酸，RD-2b位于螺旋结构域的31个氨基酸残基。与CLOCK：BMAL1异源二聚体的相互作用需要RD-2a或RD-1，CRY的核转位需要RD-1或RD-2b。这两种功能都是转录抑制因子活性的先决条件。还鉴定了RD-2b区的功能性核定位信号。该序列在包括mCRY1在内的阻遏型晶体中非常保守。MCRY1的核定位信号突变降低了其核定位的程度。这些发现表明，核定位和与Clock：BMAL异源二聚体的相互作用对于CRY的转录抑制是必不可少的。
Mouse mCRY1 and zebrafish zCRY1a and zCRY3 belong to the DNA photolyase/Cryptochrome family. mCRY1 and zCRY1a repress CLOCK:BMAL1-mediated transcription, whereas zCRY3 does not. Reciprocal chimeras between zCRY1a and zCRY3 were generated to determine the zCRY1a regions responsible for nuclear translocation, interaction with the CLOCK:BMAL1 heterodimer, and repression of CLOCK:BMAL1-mediated transcription. Three regions, RD-2a-(126–196), RD-1-(197–263), and RD-2b-(264–293), were identified. Proteins in this family consist of an N-terminal α/β domain and a C-terminal helical domain connected by an interdomain loop. RD-2a is within this loop, RD-1 is at the N-terminal 50 amino acids, and RD-2b at the following 31 amino acid residues of the helical domain. Either RD-2a or RD-1 is required for interaction with the CLOCK: BMAL1 heterodimer, and either RD-1 or RD-2b is required for the nuclear translocation of CRY. Both of these functions are prerequisites for the transcriptional repressor activity. The functional nuclear localizing signal in the RD-2b region also was identified. The sequence is well conserved among repressor-type CRYs, including mCRY1. Mutations in the nuclear localizing signal of mCRY1 reduce the extent of its nuclear localization. These findings show that both nuclear localization and interaction with the CLOCK:BMAL heterodimer are essential for transcriptional repression by CRY.
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影响因子：
56.9
作者：
PARK, HW;KIM, ST;DEISENHOFER, J
通讯作者：
DEISENHOFER, J
影响因子：
2.9
作者：
Hsu, DS;Zhao, XD;Sancar, A
通讯作者：
Sancar, A
DOI：
10.1073/pnas.96.21.12114
发表时间：
1999-10-12
影响因子：
11.1
作者：
Vitaterna, MH;Selby, CP;Sancar, A
通讯作者：
Sancar, A
影响因子：
16
作者：
Brudler, R;Hitomi, K;Getzoff, ED
通讯作者：
Getzoff, ED
影响因子：
56.9
作者：
Griffin, EA;Staknis, D;Weitz, CJ
通讯作者：
Weitz, CJ