HMGB binding to DNA: Single and double box motifs
HMGB binding to DNA: Single and double box motifs
复制标题
DOI：
10.1016/j.jmb.2007.09.073
复制
发表时间：
2007-12-07
影响因子：
5.6
通讯作者：
Williams, Mark C.
中科院分区：
文献类型：
--
作者：
McCauley, Micah J.;Zimmerman, Jeff;Williams, Mark C.
高迁移率基团 (HMG) 蛋白是核蛋白，据信可通过改变核酸的灵活性来显着影响 DNA 相互作用。 B 组 (HMGB) 蛋白含有 HMG 盒结构域，已知可与 DNA 小沟结合，无序列特异性，轻微插入碱基对并诱导 DNA 螺旋轴强烈弯曲。双光束光镊系统用于在不存在或存在人 HMGB2 单盒衍生物 [HMGB2(boxA)] 和大鼠 HMGB1 双盒衍生物 [HMGB1(boxA +box B)] 的情况下延伸双链 DNA (dsDNA)。据观察，单盒结构域减少了双螺旋的持久长度，产生平均弯曲角度为 99+/-9 度的尖锐 DNA 弯曲，并且在非常高的浓度下，稳定 dsDNA 防止变性。双盒蛋白包含两个由柔性系链连接的连续 HMG 盒结构域。该蛋白质还可以缩短 DNA 持久长度，诱导 77+/-7 度的平均弯曲角度，并在显着较低的浓度下稳定 dsDNA。这些结果表明，单盒和双盒蛋白增加了 DNA 的灵活性和稳定性，尽管双盒蛋白的两种效果都是在低得多的蛋白浓度下实现的。此外，在低浓度下，单盒蛋白可以改变 DNA 的灵活性而不稳定 dsDNA，而在较高浓度下的稳定性可能通过协作结合模式实现。 (C) 2007 Elsevier Ltd. 保留所有权利。
High mobility group (HMG) proteins are nuclear proteins believed to significantly affect DNA interactions by altering nucleic acid flexibility. Group B (HMGB) proteins contain HMG box domains known to bind to the DNA minor groove without sequence specificity, slightly intercalating base pairs and inducing a strong bend in the DNA helical axis. A dual-beam optical tweezers system is used to extend double-stranded DNA (dsDNA) in the absence as well as presence of a single box derivative of human HMGB2 [HMGB2(boxA)] and a double box derivative of rat HMGB1 [HMGB1(boxA +box B)]. The single box domain is observed to reduce the persistence length of the double helix, generating sharp DNA bends with an average bending angle of 99+/-9 degrees and, at very high concentrations, stabilizing dsDNA against denaturation. The double box protein contains two consecutive HMG box domains joined by a flexible tether. This protein also reduces the DNA persistence length, induces an average bending angle of 77+/-7 degrees, and stabilizes dsDNA at significantly lower concentrations. These results suggest that single and double box proteins increase DNA flexibility and stability, albeit both effects are achieved at much lower protein concentrations for the double box. In addition, at low concentrations, the single box protein can alter DNA flexibility without stabilizing dsDNA, whereas stabilization at higher concentrations is likely achieved through a cooperative binding mode. (C) 2007 Elsevier Ltd. All rights reserved.