Notes on Membranes and Membrane Proteins

Four Key Properties of Biomembranes:
- Fluid: Allows for movement and flexibility within the membrane structure.
- Closed Compartment: Membranes enclose environments, defining cellular boundaries.
- Semi-permeable: Regulates the passage of substances in and out of cells.
- Asymmetric: Composition differs between inner and outer leaflets; specific proteins and lipids are distributed non-uniformly.

Components:
- Lipids: Key structural component, primarily phospholipids that form bilayers.
- Sterols: Cholesterol modulates fluidity and stability of membranes.
- Proteins: Integral, lipid-linked, and peripheral proteins contribute to various functions, including transport and signaling.
Functionality: Membranes facilitate localized specialization of cellular functions.
Amphipathicity of Phospholipids: Causes them to arrange in a bilayer in an aqueous environment due to hydrophobic and hydrophilic interactions.

Nature of Fluids:
- Two-dimensional fluids: Molecules move freely within the plane of the membrane.
- Rapid lateral diffusion: Allows lipids and proteins to move in the same leaflet.
- Slow transverse (flip-flop): Rare movement between inner and outer leaflets.
Factors Affecting Fluidity:
- Fatty Acid Length: Longer chains increase viscosity.
- Cis Double Bonds: Introduce kinks, enhancing fluidity.
- Temperature: Increased temperature generally promotes fluidity.

Fluorescence Recovery After Photobleaching (FRAP):
- Up to 50% of membrane components can be immobile.
- Diffusion rates in plasma membranes are 10 times slower than in pure lipid bilayers due to protein interactions.

Structure:
- Plasma Membrane: Internal face interacts with the cytosol, defining inner spaces of the cell.
- Vesicle Membrane: External face interacts with the surrounding environment.

Permeability Characteristics:
- Small, uncharged, or hydrophobic molecules pass freely.
- Large, hydrophilic, or charged molecules are restricted and require specialized transport mechanisms.

Phospholipid Composition:
- Differences exist between leaflets with distinct lipid and protein content.
- Carbohydrates are exclusive to the exoplasmic face.
Membrane Protein Types:
1. Integral Proteins: Span the membrane and possess distinct domains.
2. Lipid-Linked Proteins: Anchored to the membrane by lipid modifications.
3. Peripheral Proteins: Associate non-covalently with membrane surfaces via interactions.

Properties:
- Asymmetrical with three domains:
- Cytoplasmic (Hydrophilic): Contains charged amino acids like Arg and Lys.
- Transmembrane (Hydrophobic): Typically forms α helices or β barrels.
- Exoplasmic (Hydrophilic): Often glycosylated, contributing to cell recognition and signaling.

Anchors:
- GPI anchors involve sugar residues sticking out into the extracellular space.
- Acylation of proteins attaches them to the membrane, allowing some mobility.

Binding Mechanisms:
- Interact through non-covalent forces such as ionic interactions, hydrogen bonds, and van der Waals forces.
- Facilitate connections between the cytoskeleton and membrane.

Topogenic Sequences: Enable proper insertion and orientation of membrane proteins.
- N-terminal Signal Sequence: Directs protein to the ER.
- Stop-transfer/membrane anchor (STA) Sequence: Halts the transfer to help anchor the protein within the membrane.
- Internal Signal-anchor (SA) Sequence: Secures proteins at specific membrane locations.

Type I:
- N-terminal signal sequence followed by a stop-transfer membrane anchor creating a single transmembrane domain with a luminal N-terminus.
Type II and III:
- Both have internal signal-anchor sequences determining orientation based on positively charged amino acids.
Type IV:
- Characterized by multiple transmembrane domains involving alternating signal-anchor and stop-transfer sequences.

Visual representation of topogenic sequences showing the orientation and interaction sites for various types of membrane proteins is crucial for understanding membrane protein synthesis and insertion mechanisms.