Peripheral Membrane Proteins

Peripheral membrane proteins vary in shape and size. Due to the amphipathic nature of phosphoglycerides, peripheral proteins do not have a hydrophobic region of amino acids. However, they have lots of hydrophilic amino acids exposed on their surface.

Although they do not penetrate the cell membrane, they play a vital role in the proper functioning of the cell.

1. Transporting Molecules

They allow the entry and exit of many molecules within and outside the cell. Electron transport chain proteins, such as cytochrome c, cupredoxins, high potential iron protein, adrenodoxin reductase, and flavoproteins, are all peripheral proteins transferring electrons from one protein to another. Without cytochrome c, the proteins responsible for generating energy would not obtain the electrons necessary for generating energy in mitochondria.

Without cytochrome c, damaged cells will not undergo cell death, causing them to become cancerous. Usually, a damaged cell produces cytochrome c from the membranes of the mitochondria, activating a cascade protein series and causing apoptosis. Thus cytochrome c being a peripheral membrane, acts as a good wingman.

Some peripheral proteins transport small hydrophobic molecules such as phosphatidylinositol, tocopherol, gangliosides, glycolipids, sterol derivatives, retinol, fatty acids, water, macromolecules, red blood cells, phospholipids, nucleotides.

2. Communication

Besides transporting, peripheral membrane proteins help communicate within a cell or adjacent bacterial cells in a colony. On stimulating the peripheral proteins, they activate the integral proteins, which then transfer the message to another peripheral protein, generating a target response.

Similarly, peripheral proteins create chain reactions, stimulating a response from the DNA or other cell organelles. It helps the cell to grow, react to danger, or release toxins that help to communicate with nearby cells.  

Some polypeptide hormones, antimicrobial peptides, and neurotoxins accumulate at the membrane and interact with the target receptors, which are peripheral proteins.

3. Anchoring Membranes

Peripheral proteins anchor the cell and intracellular membranes (mitochondrial membranes) by binding to the exterior hydrophilic lipid molecules and the integral membrane proteins. The amino acid sequence of these proteins is such that they hang out on either side of the membrane. They attach loosely to integral membrane proteins or phosphoglyceride lipid molecules through hydrogen bonds.

4. Providing Support

They form the point of attachment of the cytoskeleton and the extracellular matrix to the cell membrane. Thus, indirectly peripheral proteins help cells to maintain cell shape and size. Since the cytoskeleton also moves the products of metabolism throughout the cell, peripheral proteins control such functions. For example, when a packaged protein from Golgi reaches the cell membrane, specific peripheral proteins recognize the package and start expelling it.

5. Acting as Enzymes

Some peripheral proteins participate in the metabolism of different membrane components, such as lipids (phospholipases), cell wall oligosaccharides (glycosyltransferase), or proteins (signal peptidase).

Some peripheral proteins participating in other chemical reactions are phospholipase C, lipoxygenases, sphingomyelinase C, alpha toxins, and glycolate oxidase.

Some key differences between the two main types of membrane proteins are explained below.

Basis	Integral Proteins	Peripheral Proteins
1. Other Name	Intrinsic protein	Extrinsic protein
2. Location	Embedded throughout the membrane	Embedded on the inner and the outer surface of the phospholipid bilayer
3. Functions	Transport substances in and out of the cellServe as receptors, linkers, signal transducers, cell adhesion molecules, and anchorage	Serve as receptors, surface antigens, and enzymesHelp in communication within and outside the cell
4. Hydrophobic and Hydrophilic Domain	Contain both hydrophobic and hydrophilic domain	Contain only hydrophilic domain
5. Interaction with the Lipid Bilayer	Interact highly with the hydrophobic part of the lipid bilayerBinds to lipid bilayer through hydrophobic, electrostatic, or non-covalent interactions	Interact less with the hydrophobic part of the lipid bilayerOn the inner surface, it is held by the cytoskeleton
6. Membrane Constituent	Consists of almost 70% of all membrane proteins	Consists of almost 30% of all membrane proteins
7. Examples	Glycophorin, integrin, cadherin, selectins, rhodopsin, and G-protein coupled receptors	Cytochrome c, cupredoxins, and some flavoproteins
8. Purification	Difficult	Easy
9. Removal	Using detergents	Using a dilute salt solution