Protein Structure and Function: Study Notes

Biological Molecules of Cells

Categories of Biological Molecules

Cells are composed of four major categories of biological macromolecules, each with distinct roles in cellular structure and function.

• Proteins – Focus of this chapter; perform a wide variety of cellular functions.

• Nucleic Acids – Store and transmit genetic information (covered in Chapter 4).

• Carbohydrates – Provide energy and structural support (covered in Chapter 5).

• Lipids – Form membranes and store energy (covered in Chapter 6).

These macromolecules are assembled from smaller subunits through processes such as dehydration synthesis and are essential for the structure and function of living organisms.

Introduction to Proteins

Proteins as Essential Macromolecules

Proteins are the most abundant and versatile macromolecules in living systems. They are polymers made from 20 different amino acids, each with unique side chains, allowing for immense diversity in structure and function.

• Amino acids are the building blocks of proteins.

• Amino acids were discovered in Stanley Miller's experiment, found in meteorites, and likely abundant during chemical evolution.

• To be considered the origin of life, a molecule must possess three attributes: information, replication, and evolution.

Amino Acids and Their Polymerization

Structure of Amino Acids

All amino acids share a common core structure, which determines their chemical properties and reactivity.

• Composed of a central carbon atom (α-carbon) bonded to:

  • Hydrogen atom (H)

  • Amino group (NH2)

  • Carboxyl group (COOH)

  • R group (side chain) – variable among the 20 amino acids

Figure 3.1a and 3.1b: Illustrate the non-ionized and ionized forms of amino acids, respectively. In aqueous solution, amino and carboxyl groups ionize to NH3+ and COO-, which helps amino acids stay in solution and affects their reactivity.

Nature of Side Chains (R Groups)

The R group, or side chain, is what makes each amino acid unique and determines its properties.

• Some side chains contain functional groups that can participate in chemical reactions.

• Others consist only of carbon and hydrogen, making them nonpolar and hydrophobic.

Polarity and Charge of R Groups

The chemical nature of the R group affects the solubility and reactivity of the amino acid.

• Charged (acidic or basic) R groups are hydrophilic and interact with water.

• Uncharged polar R groups are also hydrophilic.

• Nonpolar R groups are hydrophobic and do not interact with water.

To determine the type of R group:

1. Does the side chain have a negative charge? (Acidic)

2. Does the side chain have a positive charge? (Basic)

3. If uncharged, does it contain an oxygen atom? (Polar)

4. If none of the above, it is nonpolar.

Example: Methionine is a nonpolar amino acid.

Polymerization of Amino Acids

Amino acids link together via peptide bonds to form polypeptides (proteins).

• Peptide bond: A covalent bond formed between the carboxyl group of one amino acid and the amino group of another through a condensation reaction.

• Polypeptides have directionality: the N-terminus (free amino group) and the C-terminus (free carboxyl group).

• Peptide bonds are rigid, but the single bonds on either side allow rotation, giving the polypeptide backbone flexibility.

Definitions:

• Peptide: Chain of fewer than 50 amino acids.

• Polypeptide: Chain of more than 50 amino acids.

• Protein: A complete, functional form of a polypeptide.

Levels of Protein Structure

Primary Structure

The primary structure of a protein is its unique sequence of amino acids. This sequence is determined by genetic information and is fundamental to all higher levels of protein structure.

• There are over 1013 possible primary structures due to the 20 different amino acids.

• Even a single amino acid change can drastically alter protein function (e.g., sickle cell hemoglobin).

Secondary Structure

Secondary structure is formed by hydrogen bonds between the carbonyl group of one amino acid and the amino group of another within the polypeptide backbone.

• Common types:

  • α-helix (alpha helix)

  • β-pleated sheet (beta sheet)

Tertiary Structure

Tertiary structure is the overall three-dimensional shape of a polypeptide, resulting from interactions among R groups and between R groups and the backbone.

• Hydrogen bonds – between polar side chains and partial charges.

• Hydrophobic interactions – nonpolar side chains cluster away from water.

• Van der Waals interactions – weak attractions between hydrophobic side chains.

• Covalent bonds – disulfide bonds between cysteine residues.

• Ionic bonds – between charged side chains.

Quaternary Structure

Quaternary structure arises when two or more polypeptide subunits interact to form a functional protein complex.

• Dimers: Proteins with two subunits (homodimers – identical; heterodimers – different).

• Macromolecular machines: Complexes of multiple proteins (e.g., ribosome).

• Protein structure is hierarchical: primary structure determines secondary, which folds into tertiary, and multiple tertiary structures form quaternary structure.

Table: Levels of Protein Structure

Level	Description	Stabilizing Bonds
Primary	Sequence of amino acids	Peptide bonds
Secondary	Local folding (α-helix, β-sheet)	Hydrogen bonds
Tertiary	Three-dimensional shape	Hydrogen, ionic, covalent (disulfide), hydrophobic, van der Waals
Quaternary	Multiple polypeptides	Same as tertiary (between subunits)

Protein Folding and Function

Folding and Stability

Proper protein folding is essential for function and is often spontaneous, driven by chemical interactions. Folded proteins are more stable (lower potential energy) than unfolded (denatured) forms. Denatured proteins lose their function.

Molecular Chaperones

Cells contain molecular chaperones that assist in protein folding and prevent inappropriate interactions. For example, heat shock proteins (e.g., Hsp90) bind to hydrophobic regions to prevent aggregation and allow proper folding.

Protein Flexibility and Regulation

Proteins are dynamic and may exist in multiple conformations. Some proteins only complete folding upon binding to specific molecules, allowing regulation of their activity.

Protein Misfolding and Disease

Misfolded proteins can be "infectious." Prions are misfolded proteins that induce normal proteins to adopt the abnormal conformation, leading to diseases such as "mad cow disease."

Protein Functions

Diversity of Protein Functions

Proteins perform a vast array of functions in cells:

• Catalysis – Enzymes speed up chemical reactions.

• Structure – Provide support and shape to cells and tissues.

• Movement – Motor proteins move cells or molecules within cells.

• Signaling – Transmit signals between cells.

• Transport – Move molecules across membranes or throughout the body.

• Defense – Antibodies protect against pathogens.

Enzymes as Catalysts

Enzymes are proteins that function as biological catalysts. They bind reactants (substrates) at a specific region called the active site, holding them in the correct orientation to facilitate chemical reactions.

Proteins and the Origin of Life

While proteins can catalyze reactions and may have formed spontaneously in early Earth conditions, they do not store genetic information. Nucleic acids are the primary molecules for information storage and replication.