2RN1

Liquid crystal solution structure of the kissing complex formed by the apical loop of the HIV TAR RNA and a high affinity RNA aptamer optimized by SELEX

Summary for 2RN1

• Entry DOI: 10.2210/pdb2rn1/pdb
• Related: 1KIS
• NMR Information: BMRB: 11014
• Descriptor: RNA (5'-R(P*GP*AP*GP*CP*CP*CP*UP*GP*GP*GP*AP*GP*GP*CP*UP*C)-3'), RNA (5'-R(P*GP*CP*UP*GP*GP*UP*CP*CP*CP*AP*GP*AP*CP*AP*GP*C)-3') (2 entities in total)
• Functional Keywords: rna kissing complex, hiv tar, high affinity rna aptamer selected by selex, liquid crystal nmr, ga base pair, rna
• Total number of polymer chains: 2
• Total formula weight: 10280.25

Authors

Van Melckebeke, H.,Devany, M.,Di Primo, C.,Beaurain, F.,Toulme, J.,Bryce, D.L.,Boisbouvier, J. (deposition date: 2007-12-05, release date: 2008-09-23, Last modification date: 2024-05-01)

Primary citation

Van Melckebeke, H.,Devany, M.,Di Primo, C.,Beaurain, F.,Bryce, D.L.,Boisbouvier, J.
Liquid-crystal NMR structure of HIV TAR RNA bound to its SELEX RNA aptamer reveals the origins of the high stability of the complex
Proc.Natl.Acad.Sci.Usa, 105:9210-9215, 2008

PubMed Abstract: Transactivation-response element (TAR) is a stable stem-loop structure of HIV RNA, which plays a crucial role during the life cycle of the virus. The apical loop of TAR acts as a binding site for essential cellular cofactors required for the replication of HIV. High-affinity aptamers directed against the apical loop of TAR have been identified by the SELEX approach. The RNA aptamers with the highest affinity for TAR fold as hairpins and form kissing complexes with the targeted RNA through loop-loop interactions. The aptamers with the strongest binding properties all possess a GA base pair combination at the loop-closing position. Using liquid-crystal NMR methodology, we have obtained a structural model in solution of a TAR-aptamer kissing complex with an unprecedented accuracy. This high-resolution structure reveals that the GA base pair is unilaterally shifted toward the 5' strand and is stabilized by a network of intersugar hydrogen bonds. This specific conformation of the GA base pair allows for the formation of two supplementary stable base-pair interactions. By systematic permutations of the loop-closing base pair, we establish that the identified atomic interactions, which form the basis for the high stability of the complex, are maintained in several other kissing complexes. This study rationalizes the stabilizing role of the loop-closing GA base pairs in kissing complexes and may help the development or improvement of drugs against RNA loops of viruses or pathogens as well as the conception of biochemical tools targeting RNA hairpins involved in important biological functions.

PubMed: 18607001
DOI: 10.1073/pnas.0712121105

Experimental method

SOLUTION NMR