Fundamentals of Molecular Biology. Part 1: Molecular Cell Biology - A. N. Ogurtsov 2011

Nucleic Acids and Proteins
Nucleic Acids

NUCLEOTIDES are linked together into a polymer chain via phosphodiester bonds (Figure 64). The nitrogenous bases do not participate in connecting the nucleotides of a single strand.

Class="center">

Figure 64 - Structure OF THE tetradeoxynucleotide 5'-d(TACG)

In natural polynucleotides, whether deoxyribopolymers or ribopolymers, the phosphoric acid residue always links the 3' and 5' hydroxyl groups of adjacent nucleosides (3'→5' linkage). Thus, polynucleotide chains possess a definite polarity, with each chain having a 5' and a 3' end.

The covalent sugar-phosphate backbone of a nucleic acid consists of monotonously alternating phosphate and pentose groups. The nucleic bases can be viewed as side chains attached at regular intervals along this backbone.

Notably, the sugar-phosphate backbone of a nucleic acid carries a negative charge because the phosphate groups are ionized at physiological pH (~7).

Complementary single-stranded nucleic acid molecules are capable of forming a double-stranded helical structure. Within this helix, adenine pairs with thymine, and guanine pairs with cytosine. Adenine is linked to thymine by two Hydrogen Bonds (A=T), while guanine is linked to cytosine by three hydrogen bonds (G≡C) (Figure 65).

Figure 65 - Diagram of Watson-Crick base-pairing via hydrogen bonds

DNA strands are antiparallel: one runs in the 3'→5' direction, and the other in the 5'→3' direction. According to THE PRINCIPLE OF complementarity, if one strand contains The nucleotide sequence 5'-TAGGCAT-3', the complementary strand must contain the sequence 3'-ATCCGTA-5' at that position. In this case, the double-stranded form appears as follows:

In such notation, the 5' end of the upper strand is always placed on the left, and the 3' end on the right.

The double-helix structure was discovered in 1954 by James Watson and Francis Crick. The most familiar visual model of the DNA double helix is that of a twisted ladder, where the transverse "steps" are complementary Base Pairs, and the "rails" form the sugar-phosphate backbone (Figure 66).

Figure 66 - Diagrams of nucleic bases and The formation of RNA and DNA. 1 - nucleic bases; 2 - Watson-Crick pairs; 3 - sugar-phosphate backbone

DNA contains adenine, thymine, cytosine, and guanine, whereas RNA contains uracil instead of thymine.

The Spatial Structure of a nucleic acid is determined by the interactions between the bases of each nucleotide. Because nucleic bases have an aromatic structure, they stack one above another in an aqueous solution. This process of forming stacks from flat cyclic organic molecules is known as base stacking (Figure 67(1)). In addition, the nucleic bases pair with each other through hydrogen bonds (Figure 67(2)).

Figure 67 - Diagram of intermolecular bonds in DNA: 1 - stacking; 2 - hydrogen bonds; 3 - sugar-phosphate backbone

This combination of Two Types of interactions—cooperative interactions that form base stacks (stacking) and perpendicular lateral interactions between nucleic bases via hydrogen bonds—forms the well-known structure of DNA Double helices and specific regions of RNA.

DNA acts as a vast archive for storing Genetic information, whereas RNA molecules transport this information from The Nucleus to the Cytoplasm and drive Protein Synthesis.

These functional differences correspond to structural differences between DNA and RNA, which are summarized in Table 3.

Table 3 - Differences between DNA and RNA

RNA is chemically more reactive because its sugar, ribose, contains a hydroxyl group, whereas deoxyribose lacks an oxygen atom. Due to the absence of this oxygen, DNA is more inert, which is crucial for its information-storage function to prevent unwanted Chemical Reactions. Types of RNA are listed in Table 4.

Now, let's outline the core structural principles of DNA.

1. Irregularity. There is a regular sugar-phosphate backbone attached to nitrogenous bases, The sequence of which is irregular.

2. Antiparallelism. DNA consists of two polynucleotide chains oriented in opposite directions, meaning the 3'-end of one strand lies opposite the 5'-end of the other.

3. Complementarity. Each nitrogenous base in one strand pairs exclusively with a strictly specific nitrogenous base in the opposite strand.

4. Presence of a regular Secondary structure. Two complementary, antiparallel polynucleotide chains form right-handed helices sharing a common axis.

Table 4 - Types of RNA

Several structural forms of the DNA double helix exist.

The B-form is the predominant conformation, featuring 10 complementary base pairs per helical turn. The planes of the nitrogenous bases are perpendicular to the helix axis, and adjacent base pairs are rotated relative to each other by 36°. The diameter of the helix is 20 Å, with purine nucleotides accounting for 12 Å and pyrimidine nucleotides for 8 Å.

The A-form consists of 11 base pairs per turn. The planes of the nitrogenous bases are tilted at a 20° angle relative to the normal of the helix axis, resulting in an inner core cavity with a diameter of 5 Å. The rise per turn is 28 Å. These exact parameters are also observed in DNA-RNA hybrid duplexes.

The C-form has a helical pitch of 31 Å, with 9.3 base pairs per turn and a tilt angle of 6° relative to the perpendicular.

All three forms—A, B, and C—are right-handed helices.

There are several other right-handed helical variants and only one left-handed helix (the Z-form). The pitch of the Z-form helix is 44.5 Å, with 12 nucleotide pairs per turn.

Neither the A-form nor the Z-form can exist in an aqueous solution without external stabilizing factors (such as Protein Stabilization or DNA Supercoiling).

Let us review the primary Functions of DNA.

1. DNA serves as the repository of genetic information, a role enabled by the existence of METABOLISM/28.html">The Genetic Code.

2. Replication and transmission of genetic information across generations of Cells and organisms. This function is accomplished through The process of replication.

3. Expression of genetic information into Proteins, as well as any Other Compounds synthesized with the aid of enzyme proteins. This function is carried out via Transcription and Translation.