Pattabiraman Nagarajan, Martinez Hugo M, Shapiro Bruce A
Advanced Biomedical Computing Center, SAIC, NCI Frederick, MD 21702, USA.
J Biomol Struct Dyn. 2002 Dec;20(3):397-412. doi: 10.1080/07391102.2002.10506858.
Recognition of an RNA loop by another RNA loop is involved in several biological functions. The dimerization of two copies of the HIV-1 genomic RNA is thought to be involved in several steps of the retroviral life cycle. It has been shown that the dimerization of the two HIV-1 RNA genomes is initiated by the so called kissing loop. The 9nt kissing loop consists of a palindromic 6nt sequence that forms Watson-Crick base-pairs at the kissing site in HIV-1. We report the results of our molecular modeling and dynamics studies on two major subtype isolates (MAL and LAI) of HIV-1 kissing loop structures. From our modeling studies, we conclude that the conformation of the loop in the monomer might be closer to the A-RNA-like conformation in order to form an initial kissing structure. This is achieved by the stacking interactions of the bases at the 3' end of the loop and by the intramolecular tertiary interactions of a single linker nucleotide. We discuss the effect of the loop size and the structural limitations on the formation of kissing loop structures. Also, we propose a possible mechanism to convert the kissing loop structure to a stable extended duplex structure without unwinding the stems.
一个RNA环对另一个RNA环的识别参与了多种生物学功能。HIV-1基因组RNA的两个拷贝的二聚化被认为参与了逆转录病毒生命周期的多个步骤。已经表明，两个HIV-1 RNA基因组的二聚化是由所谓的“亲吻环”启动的。9个核苷酸的“亲吻环”由一个回文的6个核苷酸序列组成，该序列在HIV-1的“亲吻”位点形成沃森-克里克碱基对。我们报告了对HIV-1“亲吻环”结构的两个主要亚型分离株（MAL和LAI）进行分子建模和动力学研究的结果。从我们的建模研究中，我们得出结论，单体中环的构象可能更接近A-RNA样构象，以便形成初始的“亲吻”结构。这是通过环3'端碱基的堆积相互作用以及单个连接核苷酸的分子内三级相互作用实现的。我们讨论了环大小和结构限制对“亲吻环”结构形成的影响。此外，我们提出了一种可能的机制，可将“亲吻环”结构转化为稳定的延伸双链结构，而无需解开茎。
