CELLMOL Lecture-7-Membrane-Proteins

Chapter 1: Introduction to Proteins

Membrane proteins make up the mosaic part of the membrane
Evidence for the presence of proteins in the membrane came from freeze fracture microscopy experiments
Membrane proteins can be categorized into integral membrane proteins, peripheral proteins, and lipid-anchored proteins

Freeze fracturing involves freezing a lipid bilayer and slicing it with a diamond knife
The resulting fracture often follows the plane between the two layers of the membrane lipid
The coarse and grainy appearance of membranes is attributed to proteins
Integral membrane proteins are embedded in the lipid bilayer due to their hydrophobic regions
Peripheral proteins are hydrophilic and located on the surface of the bilayer
Lipid-anchored proteins attach to the bilayer by covalent attachments to lipid molecules

Integral membrane proteins have hydrophobic regions that interact with the hydrophobic core of the lipid bilayer
They can be single-pass transmembrane proteins or multipass proteins
Transmembrane proteins can be arranged as alpha helices or beta barrels

Integral monotopic proteins are embedded in just one side of the bilayer
Transmembrane proteins span the membrane and protrude on both sides
Multi-subunit integral membrane proteins are made up of several subunits that traverse the lipid bilayer
Transmembrane proteins are anchored to the lipid bilayer by hydrophobic transmembrane segments
The polypeptide chain can span the membrane in an alpha helical conformation or as a closed beta sheet called a beta barrel

Beta barrel is a common structural motif for transmembrane proteins
- Core of the protein is made up of beta sheets woven into a barrel
- Amino acids in the core should be hydrophobic
Beta barrel structure is well suited for facilitating the transfer of materials across the membrane
Porins are specialized transport proteins that have a beta barrel structure
- Permeate the membrane and facilitate the regulated influx of solutes, such as water

Single pass membrane proteins have the C-terminus on one surface of the membrane and the N-terminus on the other
- C-terminus has the carboxylic acid functional group
- N-terminus contains the amine group
Example: Glycophorin is a single pass protein on the erythrocyte plasma membrane
- C-terminus is on the inner surface, N-terminus is on the outer surface

Multi pass membrane proteins have 2 to 20 or more transmembrane segments
Transmembrane segments are hydrophobic in nature and embedded in the membrane
Example: Band 3 protein in the erythrocyte membrane
- Has at least 6 transmembrane segments
- Functions as an anion exchange protein for the uptake of carbon dioxide
Example: Bacteriorhodopsin
- Has 7 transmembrane segments
- Functions as a light-driven pump for ATP generation in purple bacteria

Peripheral membrane proteins lack discrete hydrophobic regions and do not penetrate the lipid bilayer
Bound to the membrane surfaces through weak electrostatic forces and hydrogen bonds
Susceptible to changes in pH and ionic strength of the environment
Example: Spectrin, Anchorin, and Band 4.1 in erythrocytes
- Located on the inner surface of the plasma membrane
- Involved in preserving cell membrane integrity

Lipid anchored proteins are covalently bound to lipid molecules embedded in the bilayer
Two types: fatty acid anchored and GPI anchored
Fatty acid anchored proteins attached to saturated fatty acids (e.g., myristic acid, palmitic acid)
GPI anchored proteins covalently linked to glycosylphosphatidylinositol (GPI)
Lipid anchored proteins serve as anchoring points on the membrane surface

Membrane proteins have a variety of functions
Some are enzymes localized to specific membranes
Electron transport proteins involved in ATP synthesis and energy generation
Transport proteins facilitate the movement of nutrients across membranes
Receptors recognize and mediate the effects of chemical signals on the cell surface

Membrane proteins involved in the take and secretion of substances by endocytosis and exocytosis
Receptor-mediated endocytosis involves membrane proteins
Membrane proteins participate in targeting, sorting, and modification of proteins in the endoplasmic reticulum and Golgi complex
Membrane proteins play a role in autophagy, the digestion of a cell's own organelles or structures
Membrane-associated proteins stabilize and shape the cell membrane

Membrane proteins exhibit asymmetric distribution and localization across the membrane
Experiment using radioactive labeling confirms the asymmetric nature of membrane proteins
Lactoperoxidase experiment demonstrates that only proteins located on the exterior of a vesicle are labeled
Altering the osmolarity of the medium allows lactoperoxidase to label proteins located within the vesicle

Membrane proteins undergo glycosylation, a post-translational modification that adds sugar units
Glycosylation occurs in the endoplasmic reticulum and Golgi apparatus
Glycosylation has important roles in protein ligand recognition and organization of the extracellular matrix
Nearly half of expressed eukaryotic proteins undergo glycosylation
Two common types of glycosylation are N-linked and O-linked glycosylation

Carbohydrate groups of plasma membrane glycoproteins and glycolipids form a surface coat called glycocalyx
Glycocalyx plays a role in the recognition sites of membrane receptors involved in antibody-antigen reactions

Membrane proteins exhibit fluidity, but to a lesser extent compared to membrane lipids
Some proteins can move freely within the membrane, while others are constrained
Fusion experiments show that membrane proteins have variable diffusion rates
Membrane proteins can be restricted to specific areas of the membrane
Membrane domains can differ in protein composition and function