Lecture 33: Membranes and Protein Translocation

Lipid Bilayer Principle

Biological membrane is a lipid bilayer with proteins of various functions (enzymes, transporters) embedded in or associated with the bilayer

Dynamic System Principle

All internal membranes of cells are part of an interconnected, functionally specialized, and dynamic endomembrane system

Protein compositions

Transportation Principle

Although the lipid bilayer is impermeable to charged or polar solutes, cells of all kinds have many membrane transporters and ion channels that catalyze transmembrane movement of specific solutes

Lipid Bilayer

Phospholipids, sphingolipids, and sterols

Virtually insoluble in water

Spontaneously form microscopic lipid aggregates when mixed with water

Hydrophobic Reactions

The clustering of hydrophobic molecule surfaces in an aqueous environment to find the lowest energy environment by reducing the hydrophobic surface area exposed to water

Bilayer Formation

Lipid aggregate in which two lipid monolayers (leaflets) form a two dimensional sheet

Favored when the cross-sectional area of the head group and acyl side group chain are similar

Fluid Mosaic

Pattern Formed by individual lipid and protein units in a membrane

Pattern can change while maintaining the permeability of the membrane

Underlines the structure and function of biological membranes

Functions of Membranes

Permit shape changes that accompany cell growth and movement

Permit exocytosis, endocytosis, and cell division

Serve as molecular gatekeepers

Transporters

Move specific organic solutes and inorganic ions across the membrane

Receptors

Sense extracellular signals and trigger molecular changes in the cell

Ion Channels

Mediate electrical signaling between cells

Adhesion and Recognition Molecules

Hold neighboring cells together and help in cell communication

Single Membrane vs Double Membrane Organelles

The ER, golgi, lysosomes, small vesicles all have single membranes

The nucleus, mitochondria, and chloroplasts all have double membranes

Transbilayer Movement

Requires catalysis

Movement has a large positive free energy change

Membrane proteins (scramblases, flippase, floppase) facilitate the translocation of individual lipid molecules

Flippases Floppases and Scramblases

Flippases move from outer leaflet to cytosolic facing region

Floppases move from cytosolic to outer leaflet

Scramblases move in either direction (down its concentration gradient)

Summary of Transport Types

Nonpolar compounds can dissolve in the lipid bilayer and cross a membrane unassisted

Polar compounds and ions require a specific membrane protein carrier

Protein localization

Proteins are targeted to different cellular compartments by a variety of mechanisms

Essential for mediating all basic cellular and physiological functions

Proteins are targeted to particular cellular locations depending on their targeting sequence

Targeting Sequences

NLS: Nuclear localization sequence

MTS: Mitochondrial targeting sequence

Both are rich in positively charged amino acid residues

Post Translational Modifications

Refer to the covalent usually enzymatic modification of proteins during or after biosynthesis

PTMs increase the functional diversity of the proteome by the modifying proteins with aspects of normal cell biology and pathogenesis

Regulate protein localization and trafficking of proteins within cells

Phosphorylation

Can trigger changes in proein conformation leading to the exposure of nuclear localization or nuclear export signals

This regualtes the shuttling of proteins between the cytoplasm and nucleus

Ubiquitination

The addition of ubiquitin molecules to target proteins marks them for recognition by the proteasome leading to their timely degradation and recycling of amino acids