Building Biological Molecules: Proteins – Structure, Function, and Amino Acids

Building Biological Molecules: Proteins

Introduction

Proteins are essential macromolecules in all living organisms, responsible for a vast array of structural and functional roles. Understanding their structure and the properties of their building blocks, amino acids, is fundamental to the study of biology.

Important Biological Molecules

Major Classes of Biological Macromolecules

• Carbohydrates: Serve as energy sources and structural components. Monomers are monosaccharides, linked by glycosidic bonds.

• Proteins: Perform diverse functions including catalysis, transport, and structural support. Monomers are amino acids, linked by peptide bonds.

• Nucleic Acids: Store and transmit genetic information. Monomers are nucleotides, linked by phosphodiester bonds.

• Lipids: Not true polymers, but important for energy storage and membrane structure.

Water is the most abundant molecule in cells and is crucial for the structure and function of biological macromolecules.

Macromolecule Formation

Polymerization and Bond Formation

• Macromolecules are formed by adding subunits (monomers) to one end of a growing polymer chain.

• Dehydration reactions (condensation reactions) link monomers by removing a water molecule.

• Examples of covalent bonds in macromolecules:

  • Carbohydrates: glycosidic bonds

  • Proteins: peptide bonds

  • DNA/RNA: phosphodiester bonds

Bonding in Macromolecules

Covalent and Noncovalent Bonds

• Covalent bonds link monomers together to form the backbone of macromolecules.

• Noncovalent bonds (hydrogen bonds, ionic interactions, van der Waals forces, hydrophobic interactions) determine the 3D structure and stability of macromolecules.

• Both types of bonds are necessary for the assembly and function of large molecular complexes (e.g., ribosomes).

Protein Structure

Four Levels of Protein Structure

• Primary Structure: The linear sequence of amino acids in a polypeptide chain, held together by peptide bonds.

• Secondary Structure: Local folding patterns stabilized by hydrogen bonds, such as alpha-helices and beta-sheets.

• Tertiary Structure: The overall 3D shape of a single polypeptide, stabilized by interactions among R-groups (side chains), including hydrophobic interactions, ionic bonds, hydrogen bonds, and disulfide bridges.

• Quaternary Structure: The association of two or more polypeptide chains (subunits) into a functional protein complex.

Definitions

• Polypeptide: A single polymer chain of amino acid monomers linked by covalent peptide bonds.

• Protein: One or more polypeptides folded into a specific 3D structure with a biological function.

• Subunit: Each polypeptide in a multi-polypeptide protein complex.

• Homodimer: Protein with two identical subunits.

• Heterotetramer: Protein with four subunits of more than one type (e.g., hemoglobin: 2 alpha and 2 beta subunits).

Representations of Protein Structure

• Proteins can be visualized using different models:

  • Space-filling models: Show the overall shape and surface.

  • Ribbon diagrams: Highlight secondary structures (helices and sheets).

  • Simplified diagrams: Emphasize functional domains or subunit organization.

Functions of Proteins

Diverse Roles in the Cell

• Proteins account for more than 50% of the dry mass of most cells.

• Major functions include:

  • Catalysis (enzymes)

  • Structural support

  • Transport of molecules

  • Movement (muscle contraction, cell motility)

  • Cell communication

  • Gene expression regulation

  • Immune defense

Amino Acids: The Building Blocks of Proteins

General Structure of Amino Acids

• All amino acids share a common structure:

  • Alpha carbon (Cα): Central carbon atom

  • Amino group (–NH2)

  • Carboxyl group (–COOH)

  • Hydrogen atom

  • R group (side chain): Variable group that determines the properties of each amino acid

• At physiological pH (~7.4), the amino group is protonated (–NH3+) and the carboxyl group is deprotonated (–COO–).

Classification of Amino Acids by R Group Properties

• Nonpolar (hydrophobic) R-groups: Side chains are mostly hydrocarbons; do not interact favorably with water.

• Polar (hydrophilic) R-groups: Side chains contain electronegative atoms (O, N, S); can form hydrogen bonds with water.

• Electrically charged R-groups:

  • Acidic: Side chains have a negative charge at physiological pH (e.g., aspartic acid, glutamic acid).

  • Basic: Side chains have a positive charge at physiological pH (e.g., lysine, arginine, histidine).

Table: Classification of Amino Acids by R Group

Type	Examples	Properties
Nonpolar (hydrophobic)	Glycine, Alanine, Valine, Leucine, Isoleucine, Methionine, Phenylalanine, Tryptophan, Proline	Do not form hydrogen bonds; found in protein interiors
Polar (uncharged)	Serine, Threonine, Cysteine, Tyrosine, Asparagine, Glutamine	Form hydrogen bonds; often found on protein surfaces
Acidic (negatively charged)	Aspartic acid, Glutamic acid	Side chains carry a negative charge at pH 7.4
Basic (positively charged)	Lysine, Arginine, Histidine	Side chains carry a positive charge at pH 7.4

Peptide Bond Formation

Linking Amino Acids

• Amino acids are joined by peptide bonds through a dehydration reaction between the carboxyl group of one amino acid and the amino group of the next.

• The resulting chain is called a polypeptide.

$\text{Peptide bond formation:} \\ \ce{R1-CH(NH2)-COOH + R2-CH(NH2)-COOH ->[\text{dehydration}] R1-CH(NH2)-CO-NH-CH(R2)-COOH + H2O}$

Determinants of Protein Structure

Factors Influencing Protein Folding

• Primary structure (amino acid sequence) determines all higher levels of structure.

• Noncovalent interactions (hydrogen bonds, ionic bonds, van der Waals forces, hydrophobic interactions) stabilize secondary, tertiary, and quaternary structures.

• Environmental factors (pH, temperature, mutations) can alter protein structure and function.

Example: Sickle-Cell Disease

• A single amino acid substitution in the primary structure of hemoglobin leads to abnormal protein folding and function, causing sickle-cell disease.

Summary Table: Four Levels of Protein Structure

Level	Description	Bonds/Interactions Involved
Primary	Linear sequence of amino acids	Peptide bonds (covalent)
Secondary	Local folding into alpha-helices and beta-sheets	Hydrogen bonds
Tertiary	3D folding of a single polypeptide	Hydrogen bonds, ionic bonds, hydrophobic interactions, disulfide bridges
Quaternary	Association of multiple polypeptides	Same as tertiary (between subunits)

Key Takeaways

• Proteins are polymers of amino acids, with structure and function determined by the sequence and properties of their monomers.

• Understanding the four levels of protein structure is essential for grasping how proteins work in biological systems.

• Both covalent and noncovalent interactions are crucial for protein folding and stability.

• Alterations in primary structure (mutations) can have profound effects on protein function and organismal health.