Structure and Function of Nucleic Acids: DNA, RNA, and Proteins

Posted on Nov 10, 2024 in Biology

Structure of Nucleotides and Nucleosides

A nucleoside consists of a nitrogenous base (purine or pyrimidine) covalently linked to a five-carbon sugar (pentose, either ribose or deoxyribose) via an N-glycosidic bond. Examples of nucleosides include cytidine, uridine, adenosine, guanosine, thymidine, and inosine. Nucleosides can combine with a phosphate group (phosphoric acid: H3PO4) through the action of kinases, producing nucleotides, which are the basic building blocks of DNA and RNA molecules.

Nucleotide Structure

Each nucleotide is composed of three components:

  1. Nitrogenous Bases: Derived from aromatic heterocyclic compounds, purines, and pyrimidines.
    • Purine bases: Adenine (A) and Guanine (G). Both are part of DNA and RNA.
    • Pyrimidine bases: Thymine (T), Cytosine (C), and Uracil (U). Thymine and Cytosine are involved in DNA formation. In RNA, Cytosine and Uracil appear.
  2. Pentose Sugar: The five-carbon sugar can be either ribose (RNA) or deoxyribose (DNA).
  3. Phosphoric Acid: H3PO4. Each nucleotide can contain one (monophosphate: AMP), two (diphosphate: ADP), or three (triphosphate: ATP) phosphate groups.

Griffith’s Experiment with Diplococcus pneumoniae

Diplococcus pneumoniae is a bacterium that causes pneumonia. Two strains exist: S (smooth), virulent, and R (rough), non-virulent. Live S bacteria cause death in mice, while live R bacteria do not. Heat-killed S bacteria do not cause death, and heat-killed R bacteria also do not cause death.

Chargaff’s Rules

  1. The proportion of Adenine (A) is equal to that of Thymine (T): A = T. The A/T ratio is equal to 1.
  2. The proportion of Guanine (G) is equal to that of Cytosine (C): G = C. The G/C ratio is equal to 1.
  3. The proportion of purine bases (A + G) is equal to that of pyrimidine bases (T + C): (A + G) = (T + C). The (A + G)/(T + C) ratio is equal to 1.
  4. However, the proportion of (A + T) and (G + C) is characteristic of each species and can therefore take different values.

The Watson-Crick Double Helix Model

Watson and Crick used data from Chargaff (1950) on the relative composition of nitrogenous bases in DNA from different organisms, and X-ray diffraction studies on DNA fibers. X-ray diffraction helps determine the three-dimensional structure of DNA by analyzing how X-rays diffract off DNA fibers. The diffraction pattern provides information about the position of atoms within the DNA molecule.

X-ray diffraction revealed:

  • Purine and pyrimidine bases are stacked perpendicular to the axis of the polynucleotide chain, 3.4 Å apart.
  • The diameter of the polynucleotide is 20 Å and is helically wound around its axis. Every 34 Å, a complete turn of the helix occurs.
  • There is more than one polynucleotide chain coiled helically.

Based on these data, Watson and Crick proposed their double helix model with the following characteristics:

  1. The DNA double helix is right-handed.
  2. The two strands are intertwined in a plectonemic coil, like a corkscrew.
  3. Each strand is a chain of nucleotides linked by phosphodiester bonds, where a phosphate group forms a bridge between two successive sugar groups (3′ position of one sugar and 5′ position of the next).
  4. The two strands are held together by hydrogen bonds between the nitrogenous bases. Following Chargaff’s data, Adenine pairs with Thymine via two hydrogen bonds, and Guanine pairs with Cytosine via three hydrogen bonds.
  5. The strands are antiparallel, with inverse sequences. One strand runs 5′ to 3′, while the complementary strand runs 3′ to 5′.
  6. The diameter of the double helix is 20 Å.
  7. The bases are stacked 3.4 Å apart, perpendicular to the axis. Every 34 Å (10 bases), a complete turn of the helix occurs.
  8. The bases are in their keto configurations, complying with the A-T and G-C pairing rules.
  9. The sequence of bases can be anything; there is no restriction.

Nucleosomes

A nucleosome is the fundamental structural unit of chromatin, the form of DNA organization in eukaryotes. Nucleosomes consist of a protein core made up of an octamer of histone proteins.

Types and Functions of RNA

  1. Messenger RNA (mRNA): An exact copy of a DNA template, carrying information about the amino acid sequence.
  2. Transfer RNA (tRNA): Transports amino acids to ribosomes for protein synthesis. mRNA and tRNA recognize a particular amino acid to add to the growing polypeptide chain.
  3. Ribosomal RNA (rRNA): Part of the ribosome subunits, along with proteins. Participates in protein synthesis.
  4. Nucleolar RNA (snoRNA): The precursor and essential for ribosomal RNA synthesis.

Protein Synthesis

Initiation

In prokaryotes, initiation involves assembling the ribosome, mRNA, the first aminoacyl-tRNA (fMet-tRNA), GTP, and initiation factors. The ribosome has three sites: A, P, and E. The A site is the entry point for aminoacyl-tRNA (except fMet-tRNA, which enters the P site). The P site is where the peptidyl-tRNA forms. The E site is the exit site for deacylated tRNA. In eukaryotes, initiation begins with separate 60S and 40S subunits.

Elongation

Elongation adds amino acids to the carboxyl terminus of the growing polypeptide chain. The ribosome moves along the mRNA, and new aminoacyl-tRNAs enter the A site. Peptide bond formation is catalyzed by peptidyl transferase, a ribozyme activity of the 23S rRNA.

Termination

Termination occurs when a stop codon (UAA, UGA, or UAG) enters the A site. Release factors recognize these codons and trigger the release of the newly synthesized protein.

The Genetic Material

Nitrogenous bases are cyclic organic compounds containing two or more nitrogen atoms. They are fundamental components of nucleosides, nucleotides, cyclic nucleotides, dinucleotides, and nucleic acids. The main bases are adenine (A), guanine (G), thymine (T), cytosine (C), and uracil (U). A, T, G, and C are found in DNA, while A, U, G, and C are found in RNA.

Plasmids

Plasmids, also called vectors, are extrachromosomal circular or linear DNA molecules that replicate and transcribe independently of chromosomal DNA. They are commonly found in bacteria and sometimes in eukaryotes like yeast. Plasmids often carry genes that confer antibiotic resistance.

Nucleic Acids

Nucleic acids are macromolecules composed of nucleotides linked by phosphodiester bonds. There are two types: DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). They differ in their sugar (deoxyribose in DNA and ribose in RNA), bases (T in DNA and U in RNA), structure (double-stranded DNA and typically single-stranded RNA), and molecular mass (DNA is generally larger than RNA).