Beaurain François, Laguerre Michel
Institut Européen de Chimie et Biologie, CNRS UMR 5144, 33607 Pessac Cedex, France.
Oligonucleotides. 2003;13(6):501-14. doi: 10.1089/154545703322860816.
As in all retroviruses, human immunodeficiency virus (HIV) genomic RNA is packaged into virions as a dimer. The two copies of the genome are noncovalently linked by their 5'-ends in the dimerization initiating site (DIS), which folds as a hairpin containing an apical autocomplementary sequence. In vitro, DIS is able to dimerize in two conformations: a kissing complex and an extended dimer. Both conformations have been resolved by NMR and x-ray diffraction. Here, we report molecular dynamics (MD) studies of the two available structures for the DIS/DIS kissing complex in aqueous solution and in the presence of sodium counterions. The two structures behave in two different manners. On one hand, the NMR structure displays a very stable behavior, and the simulated structure remains very close to the starting structure. On the other hand, the structure issued from crystallography displays a more dynamic behavior, in which residues A8 and A9 are seen in a new and surprising bulge-in conformation. The transition from the bulge-out to the bulge-in conformation is analyzed, and a new and simple dimerization process is proposed.
与所有逆转录病毒一样，人类免疫缺陷病毒（HIV）基因组RNA以二聚体形式包装进病毒粒子。基因组的两个拷贝在二聚化起始位点（DIS）通过其5'端非共价连接，该位点折叠成一个包含顶端自互补序列的发夹结构。在体外，DIS能够以两种构象二聚化：一个亲吻复合体和一个延伸二聚体。这两种构象均已通过核磁共振（NMR）和X射线衍射解析。在此，我们报告了在水溶液中和存在钠离子的情况下，对DIS/DIS亲吻复合体的两种可用结构进行的分子动力学（MD）研究。这两种结构表现出两种不同的行为方式。一方面，核磁共振结构显示出非常稳定的行为，模拟结构与起始结构非常接近。另一方面，晶体学得到的结构表现出更动态的行为，其中A8和A9残基呈现出一种新的、令人惊讶的内凸构象。分析了从外凸构象到内凸构象的转变，并提出了一种新的、简单的二聚化过程。
