Proteins: Tertiary and Quaternary Structures (Amino Acids and Proteins)

Proteins: Tertiary and Quaternary Structures

Tertiary Structure of Proteins

The tertiary structure of a protein refers to its overall three-dimensional shape, which is formed by the interactions and repulsions of amino acid residues in different parts of the polypeptide chain. This structure is crucial for the protein's biological function and stability.

• Hydrophobic interactions: Occur between amino acids with nonpolar R groups, forming a nonpolar center at the interior of the protein. These residues are pushed away from the aqueous environment, stabilizing the protein's core.

• Hydrophilic interactions: Occur between polar amino acid residues and the external aqueous environment, pulling these residues to the protein's surface.

• Salt bridges: Ionic attractions between ionized R groups of polar basic and polar acidic amino acids, contributing to structural stability.

• Hydrogen bonds: Form between the hydrogen of a polar R group and the oxygen or nitrogen of another polar amino acid, further stabilizing the structure.

• Disulfide bonds: Covalent bonds formed between the sulfhydryl groups of cysteine residues, creating strong links within the polypeptide chain.

Example: The interaction between phenylalanine and valine (both nonpolar) results in hydrophobic interactions, while two cysteine residues form a disulfide bond.

Additional info: Chains of amino acids form ribbon-like alpha helices and beta pleated sheets, connected by various interactions. Polar amino acids interact with water outside the structure, while nonpolar molecules interact inside.

Quaternary Structure of Proteins

The quaternary structure is observed in biologically active proteins with two or more polypeptide chains (subunits). This structure is stabilized by the same interactions found in tertiary structures and is essential for the function of complex proteins like hemoglobin.

• Hemoglobin: A globular protein that transports oxygen in blood, consisting of four polypeptide chains (two with 141 amino acids and two with 146 amino acids).

• Each subunit contains a heme group with an iron center capable of binding an oxygen molecule.

• Subunits are held together by hydrophobic, hydrophilic, salt bridge, hydrogen bond, and disulfide bond interactions.

Additional info: The quaternary structure is composed of multiple tertiary structures, each contributing to the overall function of the protein.

Comparison: Hemoglobin vs. Myoglobin

• Function: Both carry oxygen, but hemoglobin transports oxygen in blood, while myoglobin carries oxygen in muscle.

• Molar mass: Myoglobin (17,000) vs. Hemoglobin (67,000).

• Oxygen capacity: Myoglobin carries one oxygen molecule; hemoglobin carries four.

• Structure: Both have similar tertiary structures.

Protein Structural Levels

Proteins consist of four structural levels:

• Primary structure: Sequence of amino acids (atomic level).

• Secondary structure: Alpha helices and beta sheets formed by hydrogen bonding.

• Tertiary structure: Three-dimensional folding due to R group interactions.

• Quaternary structure: Assembly of multiple polypeptide chains.

Chemistry Link to Health: Sickle-Cell Anemia

Sickle-cell anemia is caused by an abnormality in the shape of one of the hemoglobin subunits. The sixth amino acid in the beta chain, normally polar acidic glutamic acid, is replaced by valine, a nonpolar amino acid. This substitution leads to hydrophobic interactions, causing hemoglobin molecules to stick together and form insoluble fibers.

• Red blood cells change from a rounded shape to a crescent (sickle) shape, impairing oxygen transport.

• Fibers clog capillaries, causing inflammation, pain, organ damage, and low oxygen levels in tissues.

Additional info: Normal beta chain: Val, His, Leu, Thr, Pro, Glu, Glu, Lys. Sickled beta chain: Val, His, Leu, Thr, Pro, Val, Glu, Lys. The second Val replaces Glu, leading to disease.

Summary Table: Types of Interactions in Protein Tertiary Structure

Interaction Type	Participating Groups	Effect on Structure
Hydrophobic	Nonpolar R groups	Stabilizes protein core
Hydrophilic	Polar R groups & water	Stabilizes protein surface
Salt Bridge	Acidic & basic R groups	Provides ionic stability
Hydrogen Bond	Polar R groups	Stabilizes folding
Disulfide Bond	Cysteine residues	Strong covalent link

Key Equations

• Disulfide bond formation:

$\mathrm{2\;Cysteine\;\rightarrow\;Cystine\; (disulfide\; bond):\; 2\;HS\text{-}CH_2\text{-}R\;\rightarrow\;R\text{-}CH_2\text{-}S\text{-}S\text{-}CH_2\text{-}R}$

• Hemoglobin oxygen binding:

$\mathrm{Hb + 4\;O_2 \rightarrow Hb(O_2)_4}$

Relevant Image

The following image is directly relevant as it visually represents the textbook source for General, Organic, and Biological Chemistry, which covers the structures of life including proteins and their structural levels: