Nucleic acids tertiary structure

The tertiary structure of DNA is the structural level that is most relevant to 3-D reality. Traditionally, ODNs in a physiologically relevant aqueous solution are considered to be in a random-coiled ssDNA state or in the form of dsDNA helix in the presence of a complementary DNA, including the case of self-complementarity. The double helix is the dominant tertiary structure for biological DNA that can be in one of the three DNA conformations found in nature, A-DNA, B-DNA, and Z-DNA. The B-conformation described by Watson and Crick (11) is believed to predominate in cells (12). However other types of nucleic acid tertiary structures different from random or classical double-stranded helix forms can also be observed. Among them are triplexes, quadruplexes, and several other nucleic acid structures (13, 14). 

Single-stranded regions of nucleic acids provide metal ions with access to all possible binding sites in the nucleotide residues. In contrast, nucleic acid tertiary structure, while creating some restrictions on metal binding in certain regions, may also provide other sites at which donor atoms located... 

For molecular sizes that are amenable by NMR techniques, nucleic acids usually lack a tertiary fold. This fact, together with the characteristic low proton density, complicates NMR structural analysis of nucleic acids. As a result, local geometries and overall shapes of nucleic acids, whose structures have been determined by NMR, usually are poorly defined. Dipolar couplings provide the necessary long-range information to improve the quality of nucleic acid structures substantially [72]. Some examples can be found already in the literature where the successful application of dipolar couplings into structure calculation and structure refinement of DNA and RNA are reported [73-77]. 

For a 3-cm-long molecule of DNA to fit inside a cell so tiny that we can only see it with a microscope, the polynucleotide chain must be folded into a more compact form. Not only must the DNA be compacted, it must be folded in a way that allows it to cany out its main functions. The way the chain is folded defines the tertiary structure of a nucleic acid. 

In contrast, RNA occurs in multiple copies and various forms (Table 11.2). Cells contain up to eight times as much RNA as DNA. RNA has a number of important biological functions, and on this basis, RNA molecules are categorized into several major types messenger RNA, ribosomal RNA, and transfer RNA. Eukaryotic cells contain an additional type, small nuclear RNA (snRNA). With these basic definitions in mind, let s now briefly consider the chemical and structural nature of DNA and the various RNAs. Chapter 12 elaborates on methods to determine the primary structure of nucleic acids by sequencing methods and discusses the secondary and tertiary structures of DNA and RNA. Part rV, Information Transfer, includes a detailed treatment of the dynamic role of nucleic acids in the molecular biology of the cell. 

A correlation of enhanced synthesis of polyamines with rapid growth or cell proliferation has been observed 21. From a physiological point of view, polyamines are implicated as regulators of cell proliferative activity 22). It is well known that polyamines, as protonated polycations, can bind with nucleotide and nucleic acid anions 23 241 to affect biochemical reactivities and stabilize tertiary structures 25,26). 

Nucleic acids which contain only adenosine, guanosine and uridine are able to form A-U Watson-Crick pairs and G-U wobble pairs. They should be able to build up complex secondary and tertiary structures. 

The dependence of the residual dipolar coupling on the angle that the vector forms with a reference axis explains why the use of dipolar couplings makes possible the determination of the relative orientation of different domains in a multidomain protein and facilitates nucleic acid structure determination. Dipolar couplings can constitute up to 50% of the total structural data available for nucleic acids, while this number drops to 10-15% in proteins. Thus, the impact of the use of dipolar couplings on the structure determination of nucleic acids is generally more substantial than in the case of proteins. Furthermore, the presence or absence of tertiary structure in a protein or nucleic acid does not have a major influence on the number of dipolar couplings that can be measured, in contrast to the case of the NOE. 

The history of molecular biology has been a history of technological developments for determining the primary and tertiary structures of protein and nucleic acid molecules. Once the molecular structure is known, it provides clues to molecular functions. This is the principle of the structure-function relationship. Based on this principle the analysis of the amino acid sequence is performed to decipher the functional information from the sequence information. The analysis usually involves detection and prediction of empirical sequence—function relationships with additional consideration of known or predicted three-dimensional (3D) structures. Thus, the process can be represented schematically as ... 

We generally describe the structure of both synthetic and natural polymers in terms of four levels of structure primary, secondary, tertiary, and quaternary. The primary structure describes the precise sequence of the individual atoms that compose the polymer chain. For polymers that have only an average structure, such as proteins, polysaccharides, and nucleic acids, a representative chain structure is often given. 

It is worth to mention that this definition is not always consistent with the nature of the macromolecular assembly when applying to nucleic acids. For example, from all different types of quadruplex nucleic acids only quadruplex monomers are covered by lUPAC definition of tertiary structure being a single chain of DNA or RNA. However, also the quadruplexes with higher molecularity of the formed structures (dimers, tetramers) belong to this important tertiary structure family. 

Several direct methods are available to analyze the tertiary structure of ODNs like nuclear magnetic resonance (NMR) and X-ray crystallographic (XRC) techniques, which needs a sophisticated setup and infrastructure. An alternative but indirect method to study the structure and conformations of nucleic acids is circular dichroism spectroscopy (CD spectroscopy) (25, 26), where circular dichroism refers to the differential absorption of left and right circularly polarized light (27). 

The binding of a protein to nucleic acid is accomplished by weak, non-covalent interactions. The interactions are the same as those involved in the formation of the tertiary structure of a protein ... 

As in the case of protein structure (Chapter 4), it is sometimes useful to describe nucleic acid structure in terms of hierarchical levels of complexity (primary, secondary, tertiary). The primary structure of a nucleic acid is its covalent structure and nucleotide sequence. Any regular, stable structure taken up by some or all of the nucleotides in a nucleic acid can be referred to as secondary structure. All structures considered in the remainder of this chapter fall under the heading of secondary structure. The complex folding of large chromosomes within eukaryotic chromatin and bacterial nucleoids is generally considered tertiary structure this is discussed in Chapter 24. 

Depending upon chemical structure and the conformations that are possible, polysaccharides in solution may develop secondary structures such as helices, tertiary structures formed from junction zones or by double helix or triple helix unions and even quaternary structures from the cross linking of tertiary structures. Polysaccharides thus mimic proteins and nucleic acids, which are specific types of sugar-phosphoric acid copolymers. 

Researchers J, Versieck and L. Vanballenberghe (University Hospital, Ghent. Belgium) have observed, Tin has chemical properties offering potentials for a biological function, The element has a tendency to form truly covalent linkages as well as coordination complexes hence, it was hypothesized that it could well contribute to the tertiary structure of proteins or other biologically important macromolcculcs, such as nucleic acids. 

The tertiary structure of DNA is complex. DNA does not normally exist as a straight linear polymer, but as a supercoiled structure. Supercoiiing is associated with special proteins in eukaryotic organisms. Prokaryotic organisms have one continuous molecule white eukaryotes have many (e.g. humans have 46). Viruses also contain nucleic acids and their genetic material can be either DNA or RNA. 

All types of nucleic acids interact with proteins. Chromosomal DNA forms stable nonspecific complexes with structural proteins that stabilize their tertiary structure it also forms transient complexes with enzymes and regulatory proteins that modulate DNA and RNA metabolism. The gross tertiary structure of DNA in E. coli and a typical eukaryotic chromosome is described in the next section. 

The complex folded structures adopted by tRNAs illustrates the fact that nucleic acids with a properly adjusted primary sequence can adopt complex secondary and tertiary structures. Apropos of this, Francis Crick once said that transfer RNA is an RNA molecule trying to look like a protein. 

Base-stacking interactions are an important stabilizing force in nucleic acid structures. Describe how base stacking contributes to the tertiary structure of the tRNA molecule. 

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