Biological Membranes - A. N. Ogurtsov 2012

Structure and Functions of Biomembranes
Membrane Proteins
Modes of Protein-Membrane Interactions

Proteins are referred to as Membrane Proteins if they are integrated into the phospholipid bilayer or located on its surface. It is the membrane proteins that determine the specific activity of a given membrane or a specific region of that membrane.

Depending on The Cell type and the membrane's intracellular Location, protein density and composition can vary significantly. For instance, The inner mitochondrial membrane consists of 78% protein, whereas the myelin membrane contains only 18%. The high phospholipid content in the myelin membrane is precisely what provides electrical insulation for Nerve Cells from their surroundings.

Structure/19.html">The Importance of membrane proteins is underscored by the fact that roughly one-third of Yeast genes encode membrane proteins. In Multicellular Organisms, an even greater relative Abundance of membrane proteins is observed, as they are additionally required to facilitate cell-cell contacts.

The Lipid Bilayer represents a unique two-dimensional hydrophobic environment for membrane proteins. Some proteins are embedded within this layer, while others are attached to one of the outer surfaces—either the exoplasmic or the cytosolic face—of the membrane.

The domains of membrane proteins located on the exoplasmic side typically bind to other molecules, such as extracellular signaling proteins, ions, and small metabolites (e.g., glucose, Fatty acids), or connect with adhesive molecules of other cells or extracellular structures.

The domains residing within The Plasma Membrane (transmembrane domains), particularly those forming channels and pores, facilitate the Transport of Molecules into and out of the cell.

Meanwhile, the domains located on the cytosolic side of the membrane serve a wide range of Functions, spanning from anchoring the Cytoskeleton to initiating Intracellular Signaling pathways.

In many cases, both the function of novel membrane proteins and the spatial topology of their polypeptide chains can be predicted based on Sequence Homology with other well-characterized proteins.

Based on The Nature of their protein-membrane interactions, membrane Proteins can be classified into one of three types (Figure 35):

1) integral (transmembrane) proteins;

2) lipid-anchored (lipid-linked) proteins;

3) peripheral proteins.

Integral membrane proteins, also known as transmembrane proteins, span the entire membrane and consist of three distinct regions: a cytosolic, a transmembrane, and an exoplasmic domain.

The cytosolic and exoplasmic domains feature a hydrophilic surface that interacts with the aqueous environment on the cytosolic and exoplasmic sides of the membrane, respectively. These domains resemble other Water-soluble proteins in their Amino Acid Composition and Spatial Structure.

In contrast, the transmembrane region of the protein molecule contains a high proportion of hydrophobic Amino Acids on its surface, which interact with the inner hydrocarbon core of the phospholipid bilayer.

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Figure 35 - Three Types of Membrane proteins

In all currently known integral proteins, the transmembrane domain contains one or more alpha-helices or multiple beta-sheets.

Furthermore, most transmembrane proteins are glycosylated with complex, branched Oligosaccharides attached to one or more amino acid residues. In all cases, these carbohydrate chains are localized on the exoplasmic face.

Lipid-linked membrane proteins are covalently attached to one or more lipid molecules. The hydrophobic hydrocarbon chain of the lipid is embedded within one of the membrane monolayers, acting as an anchor for the lipid-linked protein. The polypeptide chain itself does not penetrate the phospholipid bilayer.

Peripheral membrane proteins do not interact with the Hydrophobic core of the phospholipid membrane. Typically, they bind to the membrane either directly via polar lipid HEAD groups or indirectly through interaction with integral membrane proteins.

Peripheral proteins are found on both the cytoplasmic and cytosolic sides of the plasma membrane.

In addition to these Three types of proteins, which associate firmly and specifically with the membrane, cytoskeletal filament proteins also associate with the cytosolic face of the membrane, usually mediated by peripheral (adapter) proteins (Figure 35).

Such association with the cytoskeleton provides mechanical support for various cellular membranes and facilitates Transmembrane Signal Transduction.

Finally, peripheral proteins on the outer surface of the plasma membrane and the exoplasmic domains of integral membrane proteins frequently attach to Components of the Extracellular matrix or to the cell walls of adjacent bacterial or plant cells.