An A-type double helix of DNA having B-type puckering of the deoxyribose rings

DNA usually adopts structure B in aqueous solution, while structure A is pr eferred in mixtures of trifluoroethanol (TFE) with water. However, the octa mer d(CCCCGGGG) and other d(C(n)G(n)) fragments of DNA provide CD spectra t hat suggest that the base-pairs are stacked in an A-like fashion even in aq ueous solution. Yet, d(CCCCGGGG) undergoes a cooperative TFE-induced transi tion into structure Ai indicating that an important part of the aqueous dup lex retains structure B. NMR spectroscopy shows that puckering of the deoxy ribose rings is of the B-type. Hence, combination of the information provid ed by CD spectroscopy and NMR spectroscopy suggests an unprecedented double helix of DNA in which A-like base stacking is combined with B-type puckeri ng of the deoxyribose rings. In order to determine whether this combination is possible, we used molecular dynamics to simulate the duplex of d(CCCCGG GG). Remarkably, the simulations, completely unrestrained by the experiment al data, provided a very stable double helix of DNA, exhibiting just the in termediate B/A features described above. The double helix contained well-st acked guanine bases but almost unstacked cytosine bases. This generated a h ole in the double helix center, which is a property characteristic for A-DN A, but absent from B-DNA. The minor groove was narrow at the double helix e nds but wide at the central CG step where the Watson-Crick base-pairs were buckled in opposite directions. The base-pairs stacked tightly at the ends but stacking was loose in the duplex center. The present double helix, in w hich A-like base stacking is combined with B-type sugar puckering, is relev ant to replication and transcription because both of these phenomena involv e a local B-to-A transition. (C) 2000 Academic Press.