van der Vaart Arjan, Lorkowski Alexander, Ma Ning, Gray Geoffrey M
Department of Chemistry, University of South Florida, 4202 E. Fowler Ave. CHE 205, Tampa, FL 33620, United States.
Curr Top Med Chem. 2017;17(6):731-741. doi: 10.2174/1568026616666160617084745.
As the heterodimerization partner for a large number of nuclear receptors, the retinoid X receptor (RXR) is important for a large and diverse set of biochemical pathways. Activation and regulation of RXR heterodimers is achieved by complex allosteric mechanisms, which involve the binding of ligands, DNA, coactivators and corepressors, and entail large and subtle conformational motions. Complementing experiments, computer simulations have provided detailed insights into the origins of the allostery by investigating the changes in structure, motion, and interactions upon dimerization, ligand and cofactor binding. This review will summarize a number of simulation studies that have furthered the understanding of the conformational dynamics and the allosteric activation and control of RXR complexes. While the review focuses on the RXR and RXR heterodimers, relevant simulation studies of other nuclear receptors will be discussed as well.
作为大量核受体的异源二聚体化伙伴，视黄酸X受体（RXR）对于众多不同的生化途径至关重要。RXR异源二聚体的激活和调节是通过复杂的变构机制实现的，这些机制涉及配体、DNA、共激活因子和共抑制因子的结合，并需要大规模且微妙的构象运动。作为补充实验，计算机模拟通过研究二聚化、配体和辅因子结合时结构、运动和相互作用的变化，对视变构作用的起源提供了详细的见解。本综述将总结一些模拟研究，这些研究进一步加深了我们对RXR复合物的构象动力学以及变构激活和控制的理解。虽然本综述重点关注RXR和RXR异源二聚体，但也将讨论其他核受体的相关模拟研究。
