BIOCHEMISTRY: A TEXTBOOK FOR UNIVERSITIES - E. S. Severin - 2004

CHAPTER 5. BIOLOGICAL MEMBRANES

II. Membrane Proteins

While the primary role of Lipids in membranes is to stabilize the bilayer, Proteins are responsible for the functional activity of membranes. Some proteins ensure The transport of specific molecules and ions, others act as Enzymes, and still others participate in linking the Cytoskeleton to the Extracellular matrix or serve as receptors for Hormones, Neurotransmitters, Eicosanoids, Lipoproteins, and nitric oxide (NO). Proteins account for 30 to 70% of membrane mass. They determine the specific Functional Characteristics of each membrane.

Structural Features and Localization of Membrane Proteins

Membrane proteins that contact the Hydrophobic core of Cell/29.html">The Lipid Bilayer must be amphiphilic. Those segments of the protein that interact with the hydrocarbon chains of Fatty acids consist predominantly of non-polar Amino Acids. The Regions of the protein located in the vicinity of polar HEAD groups are enriched with hydrophilic amino acid residues.

Membrane proteins vary in their positioning within the membrane (Fig. 5-10). They may deeply penetrate the lipid bilayer or even span it entirely—integral proteins—or attach to the membrane via various mechanisms—peripheral proteins.

Class="center">Fig. 5-10. Arrangement (localization) of proteins in membranes. Transmembrane proteins, for example: 1 — Glycophorin A; 2 — adrenaline receptor. Peripheral proteins: 3 — proteins associated with integral proteins, such as the enzyme succinate dehydrogenase; 4 — proteins attached to the polar head groups of the lipid layer, such as protein kinase C; 5 — proteins "anchored" to the membrane via a short hydrophobic terminal domain, such as cytochrome b₅; 6 — "anchored" proteins covalently linked to a membrane lipid (e.g., the enzyme alkaline phosphatase).

Peripheral Proteins

Peripheral proteins are often attached to the membrane by interacting with integral proteins or the polar regions of the lipid layer.

Proteins Forming Complexes with Integral Membrane Proteins

A number of digestive enzymes involved in the Hydrolysis of Starch and proteins are attached to the integral Proteins of the microvillar membranes of the intestine.

Examples of such complexes include sucrase-isomaltase and maltase-glucoamylase (see Chapter 7). Presumably, the association of these digestive enzymes with the membrane allows for the rapid hydrolysis of substrates and the efficient cellular uptake of hydrolysis products.

Proteins Associated with Polar Head Groups of Membrane Lipids

Polar or charged domains of a protein molecule can interact with the polar head groups of lipids via ionic and Hydrogen Bonds. In addition, numerous cytosolic soluble proteins can reversibly bind to the membrane surface under certain conditions. Sometimes, protein binding is a prerequisite for enzymatic activity. Such proteins include, for example, protein kinase C and Blood clotting factors.

Anchoring via a Membrane Anchor

An anchor can be a non-polar protein domain composed of amino acids with hydrophobic side chains. An example of such a protein is cytochrome b₅ in the ER membrane. This protein participates in redox reactions as an electron carrier (see Chapter 12).

A fatty acid residue (myristic—C₁₄ or palmitic—C₁₆) covalently linked to the protein can also function as a membrane anchor. Fatty acid-linked proteins are predominantly localized on the inner surface of The Plasma Membrane. Myristic acid is attached to the N-terminal Glycine via an amide bond. Palmitic acid forms a thioester bond with Cysteine or an ester bond with Serine and Threonine residues.

A small group of proteins can interact with the outer cell surface via a glycosylphosphatidylinositol (GPI) anchor covalently attached to the C-terminus of the protein. This anchor often serves as the sole link between the protein and the membrane, which is why Treatment with phospholipase C causes the protein to detach from the membrane.

Transmembrane (Integral) Proteins

Some transmembrane proteins span the membrane only once (e.g., glycophorin), while others have multiple segments (domains) that repeatedly cross the bilayer (Fig. 5-11).

Fig. 5-11. Integral membrane proteins containing 1 to 12 transmembrane domains. 1 - LDL receptor; 2 - GLUT-1 glucose transporter; 3 - Insulin Receptor; 4 - adrenergic receptor.

The transmembrane domains spanning the bilayer adopt an α-helical conformation. Polar amino acid residues face the interior of the globule, whereas non-polar residues contact the membrane lipids. Such proteins are described as "inside-out" compared to Water-soluble proteins, in which most hydrophobic amino acid residues are buried in the interior and hydrophilic residues are located On the surface (Fig. 5-12).

Fig. 5-12. Localization of nonpolar (open circles) and polar (filled squares) amino acids in soluble and membrane proteins.

The side chains of charged amino acids within these domains are uncharged and either protonated (–COOH) or deprotonated (–NH₂).

Glycosylated proteins

Surface proteins, or domains of integral proteins exposed on the outer surface of all membranes, are almost invariably glycosylated. Oligosaccharide residues can be attached via the amide group of asparagine or the hydroxyl groups of serine and threonine (Fig. 5-13).

Fig. 5-13. Structure OF THE low-density lipoprotein (LDL) receptor. 1 — intracellular domain; 2 — transmembrane domain; 3 — oligosaccharide residues attached to the OH groups of serine or threonine; 4 — oligosaccharide residues attached via the amide group of asparagine; 5 — LDL-binding domain.

Oligosaccharide residues protect proteins against proteolysis and participate in Ligand recognition or Cell Adhesion.

Lateral diffusion of proteins

Some membrane proteins move along the bilayer (lateral diffusion) or rotate around an axis perpendicular to its surface.

For instance, upon binding to the cytoplasmic surface of the membrane, the enzyme phospholipase A₂ can diffuse laterally across the bilayer surface and hydrolyze several thousand Phospholipids per minute until it dissociates from the membrane.

The lateral diffusion of integral proteins within the membrane is restricted due to their large size and interactions with other membrane proteins, cytoskeletal elements, or the extracellular matrix.

Unlike phospholipids, membrane proteins do not undergo transmembrane movement from one side of the bilayer to the other ("flip-flop" transitions).