Biology Chapter 4: Protein Structure

Overview of Protein Structure

• Proteins are polymers formed by amino acids linked by covalent peptide bonds.
• Native conformations are the specific 3-D shapes that enable biological activity.
• Proteins can have segments of random structure without obvious repeating patterns.

Levels of Protein Structure

• Primary Structure (1°): The linear sequence of amino acids, read from N-terminal to C-terminal.
• Secondary Structure (2°): The ordered 3-D arrangement of the polypeptide backbone, typically involving α-helices and β-sheets.
• Tertiary Structure (3°): The overall 3-D arrangement of all atoms, accounting for side chains and any prosthetic groups.
• Quaternary Structure (4°): The arrangement of multiple polypeptide subunits in relation to each other, forming larger functional complexes.

Primary Structure Insights

• Amino acid sequences dictate protein conformation and function; single amino acid changes can significantly impact biological activity (e.g., sickle-cell anemia due to Glu6 → Val substitution in hemoglobin).
• Supersecondary structures result from combinations of α- and β-strands.
  • βαβ Unit: Two parallel β-strands connected by an α-helix.
  • αα Unit: Two antiparallel α-helices, also known as a helix-turn-helix motif.
  • β-Meander: Antiparallel β-sheets linked by tight reverse turns.
  • Greek Key: A structural motif formed by a polypeptide chain looping back on itself.
• Motifs offer insights into protein folding but do not predict function.
• Domains are independently folding segments of polypeptides and units of function.

Tertiary Structure Details

• Tertiary structure incorporates all atoms, including side chains and prosthetic groups.
• Fibrous proteins have elongated, rod-like shapes, while globular proteins have more compact structures.
• Forces Stabilizing Tertiary Structure:
  • Noncovalent interactions (hydrogen bonds, hydrophobic interactions, electrostatic attractions).
  • Disulfide bonds restrict folding patterns, varying between proteins (present in chymotrypsin but absent in myoglobin).

Myoglobin Structure

• Myoglobin is composed of a single polypeptide with 153 amino acids and a heme prosthetic group within a hydrophobic pocket.
• Exhibits eight α-helical regions and no β-pleated sheets.
• Polar side chains reside on the exterior, while the interior contains mostly nonpolar side chains and polar histidines that interact with the heme group.
• The heme group binds oxygen, with its conformation significantly influenced by the protein environment.

Heme Group Characteristics

• Contains Fe(II) linked to an organic protoporphyrin IX structure, facilitating oxygen binding at the sixth coordination site.
• Four coordination sites occupied by nitrogen atoms, with the fifth occupied by the imidazole side chain of histidine residue F8.
• Oxygen has a weaker affinity than carbon monoxide; CO is a potent poison due to its high binding affinity.

Quaternary Structure Features

• Comprises proteins with multiple polypeptide chains, referred to as subunits.
• Oligomers include proteins like dimers, trimers, and tetramers, which interact primarily through noncovalent forces.
• Allosteric properties allow conformational changes in one subunit to influence neighboring subunits, critical for functional regulation.

Hemoglobin Structure

• Hemoglobin is a tetramer (α2β2), containing two α-chains and two β-chains.
• Each chain has distinct lengths (141 residues for α and 146 for β).
• Amino acid sequences of hemoglobin chains are homologous to myoglobin, illustrating evolutionary relationships among hemoproteins.

This quiz covers Chapter 4, focusing on the three-dimensional structure of proteins. It explores the different levels of protein structure, including primary, secondary, tertiary, and quaternary structures. Test your understanding of how these structures relate to protein function and biological activity.