Helix rigidity of DNA: The meroduplex as an experimental paradigm

被引:39
作者
Hagerman, KR [1 ]
Hagerman, PJ [1 ]
机构
[1] UNIV COLORADO,HLTH SCI CTR,DEPT BIOCHEM BIOPHYS & GENET,DENVER,CO 80262
关键词
nucleic acid structure; molecular evolution; RNA structure; hydrodynamics; molecular assembly;
D O I
10.1006/jmbi.1996.0393
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The intrinsic rigidity of the DNA helix is generally believed to arise primarily from vertical base-stacking interactions; however, relatively little experimental information exists regarding the relationship between the thermodynamic stability of base-stacking interactions and the mechanical rigidity imparted by such interactions. To address this issue, the solution conformations of complexes formed between adenine (A) or N-6-methyladenine ((me)A) monomer and deoxythymidylate (dT(n)) polymers of varying length (it = 40, 60, 81, and 110); have been examined. Such complexes are known to exist as extended, chiral structures in which the purine monomers exist as extensively stacked arrays. Thus, one can in principle examine the structural consequences of base-pair stack formation in the absence of any change in stoichiometric (phosphate) charge. The current approach has utilized the method of transient electric birefringence (TEB), which is highly sensitive to changes in nucleic acid conformation. Addition of millimolar concentrations of either A or (me)A to the dT(n) species leads to the formation of relatively rigid, chiral complexes whose dimensions are strictly limited by the length of the polymer strand. For adenine, the principal species appears to be [A](approximate to n/2)-dT(n) in which the polymer strand doubles back to form the two continuous strands of the complex (merotriplex). The addition of a methyl group to the N-6 position of adenine ((me)A) results in a shift to a meroduplex form, [(me)A](approximate to n)-dT(n), with an intrinsic rigidity that is nearly identical to the rigidity of the corresponding duplex, dA(n)-dT(n), despite the fact that the stoichiometric charge of the meroduplex is only one-half of that of the full duplex. The current results thus support a model in which helix rigidity is primarily due to the intrinsic resistance to deformation of base-stacking interactions; the deformation energies, as with the stacking energies themselves, are expected to be quite sequence-dependent. Phosphate-phosphate (repulsive) interactions, whose contributions are both salt-dependent and relatively sequence-independent, appear to play a secondary role in establishing helix rigidity. In particular, the DNA helix is likely to possess substantial rigidity in the absence of phosphate interactions. Thus, proteins whose interactions with DNA lead to substantial bending of the helix axis may facilitate such distortions through solvation of bases in addition to partial charge neutralization. (C) 1996 Academic Press Limited
引用
收藏
页码:207 / 223
页数:17
相关论文
共 78 条
[1]   NONENZYMATIC TRANSCRIPTION OF AN OLIGODEOXYNUCLEOTIDE-14 RESIDUES LONG [J].
ACEVEDO, OL ;
ORGEL, LE .
JOURNAL OF MOLECULAR BIOLOGY, 1987, 197 (02) :187-193
[2]   GLOBAL CONFORMATION OF A SELF-CLEAVING HAMMERHEAD RNA [J].
AMIRI, KMA ;
HAGERMAN, PJ .
BIOCHEMISTRY, 1994, 33 (45) :13172-13177
[3]  
[Anonymous], NUMERICAL RECIPES FO
[4]   ENVIRONMENT INDUCED CHANGES IN DNA-STRUCTURE [J].
BAASE, WA ;
SCHELLMAN, JA .
MAKROMOLEKULARE CHEMIE-MACROMOLECULAR SYMPOSIA, 1986, 1 :51-65
[5]   THE NUCLEIC-ACID DATABASE - A COMPREHENSIVE RELATIONAL DATABASE OF 3-DIMENSIONAL STRUCTURES OF NUCLEIC-ACIDS [J].
BERMAN, HM ;
OLSON, WK ;
BEVERIDGE, DL ;
WESTBROOK, J ;
GELBIN, A ;
DEMENY, T ;
HSIEH, SH ;
SRINIVASAN, AR ;
SCHNEIDER, B .
BIOPHYSICAL JOURNAL, 1992, 63 (03) :751-759
[6]   ELECTRIC BIREFRINGENCE AND DICHROISM OF ACRIDINE-ORANGE AND METHYLENE-BLUE COMPLEXES WITH POLYNUCLEOTIDES [J].
BRADLEY, DF ;
STELLWAGEN, NC ;
PAULSON, CM ;
OKONSKI, CT .
BIOPOLYMERS, 1972, 11 (03) :645-+
[7]   STEREOCHEMISTRY OF NUCLEIC ACIDS AND THEIR CONSTITUENTS .10. SOLID-STATE BASE-STACKING PATTERNS IN NUCLEIC ACID CONSTITUENTS AND POLYNUCLEOTIDES [J].
BUGG, CE ;
THOMAS, JM ;
RAO, ST ;
SUNDARALINGAM, M .
BIOPOLYMERS, 1971, 10 (01) :175-+
[8]   OPTICAL ACTIVITY OF SINGLE-STRANDED POLYDEOXYADENYLIC AND POLYRIBOADENYLIC ACIDS - DEPENDENCE OF ADENINE CHROMOPHORE COTTON EFFECTS ON POLYMER CONFORMATION [J].
BUSH, CA ;
SCHERAGA, HA .
BIOPOLYMERS, 1969, 7 (03) :395-&
[9]   INTERACTION + ASSOCIATION OF BASES + NUCLEOSIDES IN AQUEOUS SOLUTIONS .3. NUCLEAR MAGNETIC RESONANCE STUDY OF SELF-ASSOCIATION OF PURINE + 6-METHYLPURINE [J].
CHAN, SI ;
SCHWEIZER, MP ;
TSO, POP ;
HELMKAMP, GK .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1964, 86 (19) :4182-&