Mechanism for allosteric inhibition of an ATP-sensitive ribozyme.
We report the structural basis for the modulation of an ATP-sensitive ribozyme that was engineered by modular rational design. This allosteric ribozyme is composed of two independently functioning domains, one a receptor for ATP and the other a self-cleaving ribozyme. When fused in the appropriate fashion, the conjoined aptamer-ribozyme construct functions as an allosteric ribozyme that is inhibited in the presence of ATP. The aptamer domain remains conformationally heterogeneous in the absence of ATP, but folds into a distinct structure upon ligand binding. This ATP-induced conformational change causes a reduction in catalytic activity of the adjacent ribozyme domain due to steric interference between the aptamer and ribozyme tertiary structures. This mechanism for structural and functional modulation of nucleic acids is one of several possible mechanisms by which the function of ribozymes could be specifically controlled by small effector molecules.
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520-8103, USA.
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D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000494:Allosteric Regulation; D000495:Allosteric Site; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016337:RNA, Catalytic / Q000037:antagonists & inhibitors* / Q000737:chemistry*
D016337:RNA, Catalytic; D000255:Adenosine Triphosphate