The structural basis for molecular recognition by the vitamin B12 RNA aptamer

被引:83
作者
Sussman, D [1 ]
Nix, JC
Wilson, C
机构
[1] Univ Calif Santa Cruz, Dept Biol, Sinsheimer Labs, Santa Cruz, CA 95064 USA
[2] Univ Calif Santa Cruz, Ctr Mol Biol RNA, Sinsheimer Labs, Santa Cruz, CA 95064 USA
关键词
D O I
10.1038/71253
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous solution structures of ligand-binding RNA aptamers have shown that molecular recognition is achieved by the folding of an initially unstructured RNA around its cognate ligand, coupling the processes of RNA folding and binding. The 3 Angstrom crystal structure of the cyanocobalamin (vitamin B-12) aptamer reported here suggests a different approach to molecular recognition in which elements of RNA secondary structure combine to create a solvent-accessible docking surface for a large, complex ligand. Central to this structure is a locally folding RNA tripler, stabilized by a novel three-stranded zipper. Perpendicular stacking of a duplex on this tripler creates a cleft that functions as the vitamin B-12 binding site. Complementary packing of hydrophobic surfaces, direct hydrogen bonding and dipolar interactions between the ligand and the RNA appear to contribute to binding. The nature of the interactions that stabilize complex formation and the possible uncoupling of folding and binding for this RNA suggest a strong mechanistic similarity to typical protein-ligand complexes.
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页码:53 / 57
页数:5
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