Lec 4: Proteins, Nucleic Acids, and Their Building Blocks: Structure and Function

Proteins, Nucleic Acids, and Their Building Blocks

Protein Composition, Structure, and Function

Proteins are essential macromolecules composed of linear chains of amino acids. Their unique three-dimensional structures determine their diverse biological functions.

• Primary Structure: The linear sequence of amino acids in a polypeptide, determined by the genetic code.

• Peptide Bond Formation: Amino acids are joined by peptide bonds through a dehydration reaction (release of water).

• Protein Synthesis: Polypeptides are synthesized by ribosomes, folding as they emerge according to the sequence's atomic interactions.

• Folding Phases: Proteins fold in three main phases: secondary, tertiary, and quaternary structure formation.

• Function: The final folded structure dictates the protein's function in the cell.

Amino Acid Structure

All amino acids share a common structure but differ in their side chains, which confer unique properties.

• General Structure: Each amino acid has a central α-carbon bonded to an amino group (–NH2), a carboxyl group (–COOH), a hydrogen atom, and a variable R group (side chain).

• R Group: The R group determines the chemical nature and reactivity of each amino acid.

Classification of Amino Acids

Amino acids are classified based on the properties of their side chains (R groups):

Nonpolar, Hydrophobic Amino Acids

• Side chains are nonpolar and tend to avoid water.

• Examples: Glycine (Gly, G), Alanine (Ala, A), Valine (Val, V), Leucine (Leu, L), Isoleucine (Ile, I), Methionine (Met, M), Phenylalanine (Phe, F), Tryptophan (Trp, W), Proline (Pro, P).

Polar, Hydrophilic Amino Acids

• Side chains can form hydrogen bonds with water, making them hydrophilic.

• Examples: Serine (Ser, S), Threonine (Thr, T), Cysteine (Cys, C), Tyrosine (Tyr, Y), Asparagine (Asn, N), Glutamine (Gln, Q).

Electrically Charged, Hydrophilic Amino Acids

• Side chains are charged at physiological pH and interact with water and other charged molecules.

• Acidic (Negatively Charged): Aspartic acid (Asp, D), Glutamic acid (Glu, E).

• Basic (Positively Charged): Lysine (Lys, K), Arginine (Arg, R), Histidine (His, H).

Peptide Bond Formation and Protein Backbone

Proteins are formed by linking amino acids via peptide bonds, creating a backbone with distinct ends.

• Peptide Bond: A covalent bond formed between the carboxyl group of one amino acid and the amino group of another, releasing water.

• Directionality: Polypeptides have an amino (N-) terminus and a carboxyl (C-) terminus.

Equation for Peptide Bond Formation:

$\text{Amino acid}_1 + \text{Amino acid}_2 \rightarrow \text{Dipeptide} + H_2O$

Levels of Protein Structure

Protein structure is organized into four hierarchical levels:

• Primary Structure: The unique sequence of amino acids.

• Secondary Structure: Local folding patterns such as α-helices and β-pleated sheets, stabilized by hydrogen bonds.

• Tertiary Structure: The overall three-dimensional shape of a single polypeptide, stabilized by interactions among R groups (hydrophobic interactions, ionic bonds, disulfide bridges, hydrogen bonds).

• Quaternary Structure: The association of multiple polypeptide chains into a functional protein complex (e.g., hemoglobin).

Example: Insulin Structure

Insulin is a protein composed of two polypeptide chains linked by disulfide bonds, illustrating quaternary structure.

• Disulfide Bonds: Covalent bonds between cysteine residues stabilize the protein's structure.

• Function: Insulin regulates blood glucose levels.

Protein Folding and Misfolding

Protein folding is a spontaneous process driven by the sequence of amino acids and their interactions. Misfolded proteins can lead to diseases.

• Folding: Occurs as the polypeptide is synthesized, typically from the N- to C-terminus.

• Domains: Large polypeptides may have independently folded regions called domains.

• Misfolding: Genetic mutations can cause misfolding, sometimes resulting in toxic protein aggregates (e.g., in neurodegenerative diseases).

Nucleic Acids and Their Constituent Bases

Nucleic acids (DNA and RNA) are polymers of nucleotides that store and transmit genetic information.

• Structure: DNA is typically a double helix with antiparallel strands; RNA is usually single-stranded.

• Bases: Purines (adenine, guanine) pair with pyrimidines (thymine/uracil, cytosine) via hydrogen bonds.

• Base Pairing: In DNA, A pairs with T (2 H bonds), G pairs with C (3 H bonds). In RNA, uracil (U) replaces thymine.

• Backbone: Sugar-phosphate backbone formed by phosphodiester bonds between 3' and 5' carbons of sugars.

DNA Replication and Information Flow

Genetic information flows from DNA to RNA to protein, a process known as the central dogma of molecular biology.

• Replication: DNA strands unwind at the replication fork; each serves as a template for synthesis of a complementary strand in the 5' to 3' direction.

• Transcription: One DNA strand is transcribed into RNA by RNA polymerase, also in the 5' to 3' direction.

• Translation: Ribosomes read mRNA in the 5' to 3' direction to synthesize polypeptides from the N- to C-terminus.

• Leading and Lagging Strands: During replication, the leading strand is synthesized continuously, while the lagging strand is synthesized discontinuously in Okazaki fragments.

Summary Table: Comparison of DNA and RNA

Feature	DNA	RNA
Sugar	Deoxyribose (lacks 2' OH)	Ribose (has 2' and 3' OH)
Bases	A, T, G, C	A, U, G, C
Strandedness	Double-stranded (usually)	Single-stranded (usually)
Function	Genetic information storage	Information transfer, catalysis

Central Dogma Equation:

$\text{DNA} \xrightarrow{\text{transcription}} \text{RNA} \xrightarrow{\text{translation}} \text{Protein}$

Example: During cell division, DNA replication ensures genetic information is accurately passed to daughter cells. Errors in replication or protein folding can lead to genetic diseases.

Additional info: The images in the slides depict cell division and the cytoskeleton, highlighting the importance of proteins in cellular structure and function.