Protein Structure, Function, and Synthesis: Study Notes

Protein Structure, Function, and Synthesis

Introduction to Proteins

Proteins are essential macromolecules that play a central role in nearly all biological processes. They are highly diverse, found throughout all living organisms, and are responsible for mediating a wide variety of cellular reactions and functions.

• Diversity: Proteins vary greatly in structure and function, enabling them to participate in numerous cellular activities.

• Function: Proteins act as enzymes, structural components, signaling molecules, and transporters, among other roles.

• Ubiquity: Proteins are present in all cells and are vital for life.

Amino Acids: The Building Blocks of Proteins

Structure of Amino Acids

Amino acids are the monomeric units that make up proteins. Each amino acid contains a central carbon atom (the alpha carbon) bonded to four different groups:

• Amino group (–NH2): Acts as a base and can accept a proton.

• Carboxyl group (–COOH): Acts as an acid and can donate a proton.

• Hydrogen atom: A single hydrogen bonded to the alpha carbon.

• R group (side chain): The variable group that determines the identity and properties of the amino acid.

All amino acids share the same basic structure except for the R group, which is unique for each amino acid.

The Role of the R Group

The R group (side chain) of an amino acid determines its chemical properties and influences how the amino acid interacts with others in a protein chain. These interactions affect protein folding and the three-dimensional shape of the protein, which in turn determines its function.

• Hydrophobic R groups: Tend to cluster away from water, often found in the interior of proteins.

• Hydrophilic R groups: Interact well with water, often found on the protein surface.

• Acidic and basic R groups: Can form ionic bonds and are typically hydrophilic.

• Polar and nonpolar R groups: Affect solubility and protein interactions.

Classification of Amino Acids

Amino acids can be classified based on the properties of their R groups:

• Nonpolar (hydrophobic): R groups are mostly hydrocarbons.

• Polar (hydrophilic): R groups contain electronegative atoms (O, N, S).

• Acidic: R groups contain a carboxyl group and are negatively charged at physiological pH.

• Basic: R groups contain an amino group and are positively charged at physiological pH.

Special Amino Acids

• Glycine: Smallest amino acid; provides flexibility to protein structures.

• Proline: Contains a cyclic R group; introduces kinks or bends in protein chains.

• Cysteine: Contains a thiol group; can form disulfide bonds, stabilizing protein structure.

Peptide Bonds and Polypeptides

Amino acids are linked together by peptide bonds to form polypeptides (protein chains). A peptide bond is a covalent bond formed through a dehydration synthesis reaction, where a molecule of water is removed:

• Peptide bond formation: The carboxyl group of one amino acid reacts with the amino group of another, releasing water and forming a bond.

Peptide bonds are shorter than typical single bonds and restrict rotation, contributing to the protein's overall structure.

The Four Levels of Protein Structure

Primary Structure

The primary structure of a protein is the linear sequence of amino acids, written from the amino (N) terminus to the carboxyl (C) terminus. The order of amino acids determines all higher levels of protein structure.

• Notation: Often represented by three-letter or one-letter abbreviations (e.g., Ala-Met-Ala-Met).

• Importance: The sequence dictates how the protein will fold and function.

Secondary Structure

The secondary structure refers to local folding patterns within a polypeptide, stabilized by hydrogen bonds between backbone atoms.

• Alpha helix (α-helix): A right-handed coil stabilized by hydrogen bonds between every fourth amino acid.

• Beta sheet (β-sheet): Sheet-like arrangement; can be parallel or antiparallel, stabilized by hydrogen bonds between adjacent strands.

Tertiary Structure

The tertiary structure is the overall three-dimensional shape of a single polypeptide chain, resulting from interactions among R groups and between R groups and the peptide backbone.

• Stabilizing forces: Hydrogen bonds, ionic bonds, van der Waals forces, disulfide bridges, and hydrophobic interactions.

• Functional form: The tertiary structure determines the protein's function unless it is part of a multi-subunit complex.

All of these forces (hydrogen bonding, ionic bonding, van der Waals forces, covalent bonding) can contribute to tertiary structure.

Quaternary Structure

The quaternary structure is the arrangement of multiple polypeptide subunits in a multi-subunit protein. Not all proteins have quaternary structure.

• Examples: Hemoglobin (four subunits), DNA polymerase (multiple subunits).

Protein Structure Determines Function

The specific shape of a protein is critical for its function. The arrangement of amino acids and the resulting three-dimensional structure create active sites and interaction surfaces necessary for biological activity.

• Active sites: Pockets formed by the protein's structure where substrates bind and reactions occur (in enzymes).

• Protein-protein interactions: Determined by the distribution of R groups on the protein surface.

Changes in the environment (e.g., pH, temperature) or mutations in the amino acid sequence can alter protein structure and function. Chaperone proteins assist in proper protein folding and help prevent denaturation.

Special Case: Histone Protein Evolution

Histone proteins, which package DNA in cells, are among the most slowly evolving proteins. For example, histone H4 differs by only two amino acids between cows and peas (out of about 100 amino acids). This slow evolution is due to the critical function of histones in binding negatively charged DNA, requiring a high content of basic amino acids (lysine and arginine).

• Conservation: Amino acids in histone proteins cannot be replaced without disrupting structure and function.

The Central Dogma

The central dogma of molecular biology describes the flow of genetic information:

• DNA → RNA → Protein

• Genetic information is transcribed from DNA to RNA and then translated into protein.

Summary Table: Levels of Protein Structure

Level	Description	Stabilizing Forces
Primary	Linear sequence of amino acids	Peptide bonds
Secondary	Local folding (α-helix, β-sheet)	Hydrogen bonds
Tertiary	3D folding of a single polypeptide	Hydrogen bonds, ionic bonds, van der Waals forces, disulfide bridges
Quaternary	Assembly of multiple polypeptides	Same as tertiary (between subunits)

Key Equations

• Peptide bond formation (dehydration synthesis):

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

• General structure of an amino acid:

$\mathrm{H_2N{-}CHR{-}COOH}$

Additional info: The notes have been expanded to include standard definitions, examples, and context for General Chemistry students, as well as a summary table for clarity.