Ennifar Eric, Paillart Jean-Christophe, Bernacchi Serena, Walter Philippe, Pale Patrick, Decout Jean-Luc, Marquet Roland, Dumas Philippe
Architecture et réactivité de l'ARN, UPR 9002 CNRS, Institut de Biologie Moléculaire et Cellulaire, 15 rue René Descartes, 67084 Strasbourg, France.
Biochimie. 2007 Oct;89(10):1195-203. doi: 10.1016/j.biochi.2007.03.003. Epub 2007 Mar 12.
Dimerization of the genomic RNA is an important step of the HIV-1 replication cycle. The Dimerization Initiation Site (DIS) promotes dimerization of the viral genome by forming a loop-loop complex between two DIS hairpins. Crystal structures of the DIS loop-loop complex revealed an unexpected and strong similitude with the bacterial 16S ribosomal aminoacyl-tRNA site (A site), which is the target of aminoglycoside antibiotics. As a consequence of these structural and sequence similarities, the HIV-1 DIS also binds some aminoglycosides, not only in vitro, but also ex vivo, in lymphoid cells and in viral particles. Crystal structures of the DIS loop-loop in complex with several aminoglycoside antibiotics provide a detailed-view of the DIS/drug interaction and reveal some hints about possible modifications to increase the drug affinity and/or specificity.
基因组RNA的二聚化是HIV-1复制周期中的一个重要步骤。二聚化起始位点（DIS）通过在两个DIS发夹之间形成环-环复合物来促进病毒基因组的二聚化。DIS环-环复合物的晶体结构显示出与细菌16S核糖体氨酰-tRNA位点（A位点）存在意想不到的高度相似性，而A位点是氨基糖苷类抗生素的作用靶点。由于这些结构和序列上的相似性，HIV-1 DIS不仅在体外，而且在体内的淋巴细胞和病毒颗粒中也能结合一些氨基糖苷类药物。与几种氨基糖苷类抗生素形成复合物的DIS环-环晶体结构提供了DIS/药物相互作用的详细视图，并揭示了一些关于可能的修饰以增加药物亲和力和/或特异性的线索。
