2025 Lecture 8_BIOC212_Maria Vera Ugalde

Lecture 8: Membrane Proteins – 2

• Course: BIOC 212, Winter 2025, Instructor: Maria Vera Ugalde

Summary of Lecture 7

• Key components include differences and structures of lipid and protein molecules.

Key Molecular Structures

Fatty Acid Tails

• Phosphatidyl-Ethanolamine (A)

• Phosphatidyl-Serine (B)

• Phosphatidyl-Choline (C)

• Sphingomyelin (D)

• Visual references in figures from Molecular Biology of the Cell, 4th and 5th Editions

Lipid Bilayer

• Composed of:

  • Polar head groups: Hydrophilic regions

  • Nonpolar hydrocarbon tails: Hydrophobic regions

  • Typical thickness: 5 nm

Fluidity and Rigidity

• Fatty Acid Structure:

  • Saturated: More flexible

  • Unsaturated: Increased fluidity due to cis-double bonds

  • Cholesterol: Increases rigidity of fatty acid tails

Comparison of Membrane Components

• Phospholipids: Larger polar structures, hydrophobic end, charged ends; compared to:

  • Amino Acids: Varying polarity and hydrophobicity,

  • Glycolipids: Polar, some acidic charges,

  • Cholesterol: Weak polarity, very hydrophobic.

  • Free Fatty Acids: Charged carboxyl, hydrophobic regions.

Outline of Membrane Proteins

• Types of membrane proteins:

  • Integral Membrane Proteins

  • Lipid-Anchored Proteins

  • Peripheral Membrane Proteins

• Integration/Anchoring of proteins into membranes:

  • Integral Proteins:

    • Transmembrane helices

    • Transmembrane barrels

  • Lipid-Aanchored Proteins:

    • Acylation and prenylation

    • Glycosyl-phosphatidyl-inositol (GPI) anchors

Structure and Function of Membrane Proteins

• Membrane protein sequence influences structure, function, and localization.

• Membrane protein structure requires lipid interactions for proper localization.

• Distinguishing solubility:

  • Soluble Proteins: Not associated with membranes.

Integral Membrane Proteins

• Anchored tightly via hydrophobic interactions:

  • Contains one or more transmembrane α-helices.

  • Can possess transmembrane β-barrels.

Lipid-Anchored vs Peripheral Membrane Proteins

Lipid-Anchored Proteins

• Covalently linked to lipids or fatty acids.

• Anchor strength depends on the type and number of lipids.

Peripheral Membrane Proteins

• Attached through non-covalent interactions:

  • Strong interactions with integral proteins.

  • Weaker interactions with lipid head groups.

Protein Functionality

• Transmembrane Proteins:

  • Function in both cellular compartments (e.g., receptors, transporters).

Transmembrane Helices

• Most common mechanism of attachment:

  • Amino acid side chains indicate hydrophobicity,

  • Internal hydrogen bonds stabilize helices.

Amino Acids and Side Chains

• Uncharged Polar Side Chains:

  • Ex: Asparagine (Asn) and Glutamine (Gln).

• Nonpolar Side Chains:

  • Ex: Alanine, Valine, Glycine, etc.

• Acidic and Basic Side Chains:

  • Specific structures influence interactions with membranes.

Single and Multiple TM Helices

• Proteins may contain:

  • One or more helical transmembrane domains (e.g., single-pass and multi-pass).

  • TM helices contribute to hydrophobic characteristics necessary for function.

Hydrophobicity Index

• Different scales assess amino acid properties.

• Key reference for understanding membrane protein behavior.

Transmembrane β-Barrels

• Formation through β-strands wrapped in a cylinder.

• Essential for some membrane proteins, providing structural integrity.

Membrane Protein Asymmetry

• Orientation determined during membrane insertion:

  • Different modifications occur in lumen/extracellular vs. cytoplasmic domains.

  • Includes disulfide bonds and glycosylation for stability.

Example: Channels and Pumps

• Mechanisms control ion and polar molecule movement:

  • Channels facilitate movement along concentration gradients.

  • Pumps require energy (ATP) to move against gradients.

Channel Proteins

• Regulate flow of ions utilizing TM helix channels.

• Pores selectively allow specific ions based on physical properties.

Example: Voltage-Gated K+ Channel

• Specific to neurons for signaling with specialized structure and control mechanisms.

ATP-Dependent Transporters

• Function by utilizing ATP for substrate transport against gradients (e.g., Na+-K+ pump).

Lipid-Anchored Proteins

• Transient or strong interaction with membranes depends on the type and number of lipid chains attached.

GPI-Anchored Proteins

• Strongly attached to membranes, exclusive to external cellular environments.

Thought Experiment

• Consider the structural implications of membrane proteins absent of membranes.