The effect of obstacles in multi-site protein target search with DNA looping

被引:8
作者
Felipe, Cayke [1 ]
Shin, Jaeoh [2 ,3 ]
Loginova, Yulia [4 ]
Kolomeisky, Anatoly B. [1 ,2 ,3 ,5 ]
机构
[1] Rice Univ, Dept Phys, Houston, TX 77005 USA
[2] Rice Univ, Dept Chem, Houston, TX 77005 USA
[3] Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 USA
[4] Moscow MV Lomonosov State Univ, Dept Chem, Moscow, Russia
[5] Rice Univ, Dept Chem & Biomol Engn, Houston, TX 77005 USA
关键词
REPRESSOR-OPERATOR INTERACTION; FACILITATED DIFFUSION; BINDING; MECHANISMS; LOCATION; KINETICS;
D O I
10.1063/1.5135917
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
Many fundamental biological processes are regulated by protein-DNA complexes called synaptosomes, which possess multiple interaction sites. Despite the critical importance of synaptosomes, the mechanisms of their formation are not well understood. Because of the multisite nature of participating proteins, it is widely believed that their search for specific sites on DNA involves the formation and breaking of DNA loops and sliding in the looped configurations. In reality, DNA in live cells is densely covered by other biological molecules that might interfere with the formation of synaptosomes. In this work, we developed a theoretical approach to evaluate the role of obstacles in the target search of multisite proteins when the formation of DNA loops and the sliding in looped configurations are possible. Our theoretical method is based on analysis of a discrete-state stochastic model that uses a master equations approach and extensive computer simulations. It is found that the obstacle slows down the search dynamics in the system when DNA loops are long-lived, but the effect is minimal for short-lived DNA loops. In addition, the relative positions of the target and the obstacle strongly influence the target search kinetics. Furthermore, the presence of the obstacle might increase the noise in the system. These observations are discussed using physical-chemical arguments. Our theoretical approach clarifies the molecular mechanisms of formation of protein-DNA complexes with multiple interactions sites. Published under license by AIP Publishing.
引用
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页数:7
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