The structural basis for molecular recognition by the vitamin B12 RNA aptamer
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作者:
Sussman, D
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Univ Calif Santa Cruz, Dept Biol, Sinsheimer Labs, Santa Cruz, CA 95064 USAUniv Calif Santa Cruz, Dept Biol, Sinsheimer Labs, Santa Cruz, CA 95064 USA
Sussman, D
[1
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Nix, JC
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机构:Univ Calif Santa Cruz, Dept Biol, Sinsheimer Labs, Santa Cruz, CA 95064 USA
Nix, JC
Wilson, C
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机构:Univ Calif Santa Cruz, Dept Biol, Sinsheimer Labs, Santa Cruz, CA 95064 USA
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
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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MEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USAMEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USA
Fan, P
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Suri, AK
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MEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USAMEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USA
Suri, AK
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Fiala, R
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MEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USAMEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USA
Fiala, R
;
Live, D
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MEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USAMEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USA
Live, D
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Patel, DJ
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MEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USAMEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USA
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MEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USAMEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USA
Fan, P
;
Suri, AK
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MEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USAMEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USA
Suri, AK
;
Fiala, R
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MEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USAMEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USA
Fiala, R
;
Live, D
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MEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USAMEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USA
Live, D
;
Patel, DJ
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MEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USAMEM SLOAN KETTERING CANC CTR, CELLULAR BIOCHEM & BIOPHYS PROGRAM, NEW YORK, NY 10021 USA