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From quadruplex to helix and back: Meta-stable states can move through a cycle of conformational changes

  作者 Mills, M; Mergny, JL; Klump, HH  
  选自 期刊  Archives of Biochemistry and Biophysics ;  卷期  2008年474-1;  页码  8-14  
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[摘要]Strand displacement cycles can be driven by sequential addition of short oligonucleotide sequences. Successive inter- and intra-molecular interactions based on the rules of Watson-Crick base pairing allow us to design self-assembling molecular systems with predictable folding pathways and conformational changes. Here we present a particular strand displacement cycle that starts from a tethered quadruplex-forming sequence from the human telomere repeat (T(2)AG(3))(4) that forms a G-quartet within a stem-loop structure. Adding an almost matching single strand converts the four-stranded section into a defective double helix. This is the first step of the cycle. The subsequent addition of a "fuel strand" removes the single strand from the loop sequence in favor of a perfect double helix. This displacement frees the hairpin-loop to go back to its initial state. Analysis of this cycle, that resembles an enzyme-substrate pathway as far as the initial state will be regained at the end of the cycle, advances our understanding of the interchanges between meta-stable states that underlie some fundamental steps in molecular biology, and allow for the construction of nano-molecular machines. (C) 2008 Elsevier Inc. All rights reserved.

 
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