2JPZ : Human telomere DNA quadruplex structure in K+ solution hybrid-2 form

  • Jixun Dai (Contributor)
  • Megan Carver (Contributor)
  • Danzhou Yang (Contributor)
  • Chandanamali Punchihewa (Contributor)
  • Roger A. Jones (Contributor)



Experimental Technique/Method:SOLUTION NMR
Release Date:2007-12-04
Deposition Date:2007-05-25
Revision Date:2011-07-13#2014-10-01
Molecular Weight:8200.27
Macromolecule Type:DNA
Residue Count:26
Atom Site Count:545

Formation of the G-quadruplex in the human telomeric sequence can inhibit the activity of telomerase, thus the intramolecular telomeric G-quadruplexes have been considered as an attractive anticancer target. Information of intramolecular telomeric G-quadruplex structures formed under physiological conditions is important for structure-based drug design. Here, we report the first structure of the major intramolecular G-quadruplex formed in a native, non-modified human telomeric sequence in K(+) solution. This is a hybrid-type mixed parallel/antiparallel-G-stranded G-quadruplex, one end of which is covered by a novel T:A:T triple capping structure. This structure (Hybrid-2) and the previously reported Hybrid-1 structure differ in their loop arrangements, strand orientations and capping structures. The distinct capping structures appear to be crucial for the favored formation of the specific hybrid-type intramolecular telomeric G-quadruplexes, and may provide specific binding sites for drug targeting. Our study also shows that while the hybrid-type G-quadruplexes appear to be the major conformations in K(+) solution, human telomeric sequences are always in equilibrium between Hybrid-1 and Hybrid-2 structures, which is largely determined by the 3'-flanking sequence. Furthermore, both hybrid-type G-quadruplexes suggest a straightforward means for multimer formation with effective packing in the human telomeric sequence and provide important implications for drug targeting of G-quadruplexes in human telomeres.
Date made available2007

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