Study Notes for MCB 250 VCAST 14 - Alpha Helices and Beta Strands/Sheets

MCB 250 - Alpha Helices and Beta Strands/Sheets

Lecturer Information

  • Course: MCB 250
  • Vcast: 14
  • Instructor: Dr. James M. Slauch
  • Department: Microbiology

Levels of Protein Structure and Nomenclature

  • Primary Structure: Sequence of amino acids in a polypeptide chain.
  • Secondary Structure: Local folding of the polypeptide into structures such as alpha-helices and beta-sheets due to hydrogen bonding.
  • Tertiary Structure: Overall 3D structure of a single polypeptide chain.
  • Quaternary Structure: Assembly of multiple polypeptide subunits into a functional complex.
  • Amino Acids in Structure: Commonly referenced amino acids include:
    • Gln (Glutamine)
    • Ala (Alanine)
    • Thr (Threonine)
    • Met (Methionine)
    • Lys (Lysine)
    • Leu (Leucine)
    • Arg (Arginine)
    • Ile (Isoleucine)
    • Glu (Glutamic acid)
    • Phe (Phenylalanine)
    • Ser (Serine)
  • Illustration Reference: Figure 4-1 depicts the formation and hierarchy of protein structures, as explained in "Molecular Biology: Principles and Practice" © 2012 W. H. Freeman and Company.

Forces Affecting Protein Structure

  • Various interactions contribute to the stability and shape of protein structures:
    • Van der Waals Bonds: Weak attractions between atoms that stabilize structure.
    • Hydrophobic Interactions: Nonpolar side chains aggregate to avoid water.
    • Cluster Stacked Rings: Arrangement of aromatic amino acids can form complexes.
    • Negatively Charged Amino Acids: Participate in ionic interactions.
    • Hydrogen Bonds: Key in maintaining secondary structure.
    • Ionic Bonds: Electrostatic interactions between charged side chains.
    • Disulfide Bonds: Covalent bonds between cysteine residues, providing stability to tertiary and quaternary structures.

Rotational Freedom of Peptide Bonds

  • Peptide Bonds: Rotate freely around the α-carbon, influencing the conformation of the polypeptide chain.
    • Energetically Unfavorable Conformations: Certain angles are not biologically viable due to steric hindrance.
  • Structure:
    • α-carbon connects to:
    • Carbonyl carbon
    • Hydrogen ()
    • Nitrogen
    • Oxygen
    • Side chain (R group)

Secondary Structure

  • Definition: Involves hydrogen bonding between the carbonyl (C=O) of one amino acid and the nitrogen (NH) of another in the peptide backbone.
  • Example: Representation of hydrogen bonding between two amino acids:
    • Amino Acid #1: Acts as hydrogen bond donor while:
    • Amino Acid #2: Acts as hydrogen bond acceptor.

The Alpha-Helix

  • Stabilization: Held together by hydrogen bonds.
  • Characteristics:
    • Turn Count: 3.6 amino acid residues per turn.
    • Hydrogen Bond Pattern: Between the backbone C=O of residue n and the NH of residue n+4.
    • Exclusions: First 4 NH and the last 4 C=O are not involved in hydrogen bonding.
    • Helix Directionality: Typically right-handed.
  • Terminology: An amino acid in a protein is referred to as a residue since it has lost a water molecule and is no longer simply an amino acid.
  • Measurement: 3.6 residues yield approximately 5.4 Å per turn, akin to Figure 4-6 representation.

R Groups in Alpha Helix

  • Orientation: R groups (side chains) extend outward from the helix core, contributing to its properties.
  • Spacing: Approximately 3.5 AAs per full turn, leading to a periodicity of around 7 Å.

Amino Acids Favorability for Helical Structures

  • Favorable Amino Acids: The sequence "MALEK" is considered favorable for forming alpha helices.
  • Disruptive Residues:
    • Proline (P): Common helix breaker due to its structure that imposes rigidity.
    • Glycine (G): Generally disfavored in helices due to high conformational flexibility.
  • Note: These are tendencies, not absolute rules that govern structure formation.

The Beta Strand and Beta Pleated Sheet

  • Beta-Pleated Sheet Configurations:
    • Antiparallel Orientation: Specific alignment where strands run in opposite directions.
    • Parallel Orientation: Strands aligned in the same direction.
  • Inter-Strand Distance: Characteristically around 7 Å for every 2 residues.
  • Directional Convention: In diagrams, arrows point from N-terminus to C-terminus as per established conventions.

Connection of Secondary Structures

  • Loops: Serve as connectors between secondary structures, varying from small (2 amino acids) to large segments that can significantly contribute to protein architecture.

Properties of Secondary Structures

  • Stability: Compact and stable characteristic shapes of proteins.
  • Packing Efficiency: Structures can easily pack together within the protein core.
  • Hydrophobicity: When a segment's side chains are hydrophobic, the folded helix or strand can be situated within a hydrophobic core or integrated into a phospholipid bilayer.
  • Practical Application: Participants are encouraged to download “ProteinOrigami.PDF” from the course website for additional structural exercises and visualization.