TAR-RNA binding by HIV-1 Tat protein is selectively inhibited by its L-enantiomer.
An oligoribonucleotide, corresponding to the Tat-interactive top half of the HIV-1 TAR RNA stem-loop, was synthesized in both the natural D- and the enantiomeric L-configurations. The affinity of Tat for the two RNAs, assessed by competition binding experiments, was found to be identical and is reduced 10-fold for both, upon replacement of the critical bulge residue U23 with cytidine. It is suggested that this interaction of the flexible Tat protein depends strongly upon the tertiary structure of a binding pocket within TAR, but not upon its handedness, and may be described by a 'hand-in-mitten' model.
Garbesi
A
A
Consiglio Nazionale delle Ricerche, I. Co. C.E.A., Bologna, Italy and Novartis Pharma Research,Department of Oncology, K-125 3.09, CH-4002 Basle, Switzerland.
Hamy
F
F
Maffini
M
M
Albrecht
G
G
Klimkait
T
T
D001667:Binding, Competitive; D015696:Gene Products, tat / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D009690:Nucleic Acid Conformation; D009843:Oligoribonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000737:chemistry*; D013237:Stereoisomerism; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D009843:Oligoribonucleotides; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus