Book of Abstracts: Albany 2003
June 17-21 2003
DNA-Metal Ion Interactions in Crystal Structures of Oligonucleotides
Crystal structures of nucleic acid molecules at high resolution often reveal the locations of mono- and divalent metal cations. For example, several Mg2+ and Ca2+ ions were observed to coordinate to the B-DNA dodecamer [d(CGCGAATTCGCG)2] in structures of the Mg- (1) and Ca-forms (2), respectively, of the oligonucleotide. In the Mg-form a Mg2+ ion was found to coordinate to the G2pC3 step adjacent to an asymmetric kink into the major groove and two further Mg2+ ions link phosphates from opposite strands across the minor groove, resulting in a marked narrowing at that site. X-ray crystallography also established binding of alkali metal ions in the minor groove of the above dodecamer at the central ApT step (3). A series of crystal structures of an A-form DNA decamer with sequence GCGTATACGC demonstrated binding of alkali and alkaline earth metal ions to the same site inside the major groove (4). In addition, a recent crystal structure at 1.5 Å resolution of a stilbene-capped DNA hairpin containing a central A4:T4 stretch revealed a Mg2+ hexahydrate bound inside the narrow A-tract minor groove (5).
Despite progress in locating metal ions in structures of DNA and analyzing their detailed binding modes it appears difficult to decide how important they are for DNA conformation (6). Are metal ions effectively ruling over the influence of DNA sequence in some cases or is metal ion binding primarily depending on DNA conformation with conformation depending on sequence? Particularly with respect to DNA bending the role of metal ions based on the structural insights have led to some contradictory interpretations. The interpretation of the influence of metal ion binding on DNA structure is further complicated by the fact that particular localizations of metal ions in a crystal can be simply due to lattice effects. For example, in the crystal structure of the above dodecamer, lattice forces may bring about the kink near one end of the duplex and the resulting particular conformation at the GpC step may then promote Mg2+ binding. Although structural analyses of oligonucleotides alone will not allow a final answer, it is likely that DNA sequence context will affect cation binding, and in turn, cation binding may have some influence on DNA conformation. We will review recent insights from high-resolution crystal structures of oligodeoxynucleotides and discuss the role of metal cations in DNA structure.
Dept. of Biological Sciences