At. Phan et al., The solution structure and internal motions of a fragment of the cytidine-rich strand of the human telomere, J MOL BIOL, 299(1), 2000, pp. 123-144
We present the solution structure of d (CCCTA(2)CCCTA(2)CCCTA(2)CCCT), a fr
agment of the vertebrate telomere which folds intramolecularly. The four cy
tidine stretches form an i-motif which includes six intercalated C.C+ pairs
and terminates with the cytidines at the 5' extremity of each stretch. Abo
ve, the second TA(2) linker loops across one of the narrow grooves, while a
t the bottom, the first and third linkers loop across the wide grooves.
At 30 degrees C, the spectra of the first and third linkers are quasi-degen
erate. Severe broadening at lower temperature indicates that this results f
rom motional averaging between at least two structures of each bottom loop,
and makes it impossible to solve the configuration of the bottom loops dir
ectly, in contrast to the rest of the structure.
We therefore turned to the modified sequence d(CCCTA(2)5mCCC-TA(2)CCCUA(2)C
CCT) in which the two base substitutions (underlined) break the quasi-symme
try between linkers 1 and 3. The three loops follow approximately the hairp
in "second pattern" of Hilbers. In the first loop, T4 is in the syn orienta
tion, whereas its analog in the third loop, U16, oriented anti, is in a cen
tral location, where it interacts with bases of both loops, thus contributi
ng to their tight association. The only motion is a syn/anti flip of A18 in
the third loop.
Returning to the telomere fragment, we show that each of the bottom loops s
witches between the structures identified in the first and third loops of t
he modified structure. The motions are concerted, and the resulting configu
rations of the bottom loop cluster present a bulge to either right (T4 syn)
or left (T16 syn). (C) 2000 Academic Press.