Lipids and proteins are the major constituents of most plasma membranes which account for approximately 50-50% each by weight, with carbohydrate portion of glycolipids and glycoproteins comprising 5 to 10% of the membrane mass. Similarly, internal organelles such as mitochondria and chloroplast that are involved in energy transduction constitute around 75% of proteins. Thus, their amount and types vary with different types of membrane. Lipid bilayer provides the structural framework of the cell membrane, while membrane proteins facilitate many biological processes such as cell adhesion, cell signaling, cell recognition, energy transduction, and cellular transport. Ion channels, transporter, receptors, and enzymes represent membrane proteins. A significant fraction (20-30%) of all genes in genomes encode for membrane proteins, and thus, these are targets and potential candidates for medicinal drug discovery.
Membrane proteins are the proteins that are adhered to or associated with the biological membrane.
Unique properties of different kinds of membranes are due to membrane proteins, and these makeup around 1/3rd of the proteins in living organisms. Most membrane proteins are free to move within the lipid bilayer due to the fluid nature of lipid, and these can also be limited to some areas of the bilayer with enzymes. The first membrane protein to be sequenced was Glycophorin. Membrane proteins are diverse in nature in terms of their structure and function.
Structure of membrane proteins
Cell membrane chiefly comprises two phospholipid layers, also known as a phospholipid bilayer which separates the external environment of the cell from that of the internal environment. Membrane proteins are embedded into phospholipid bilayers either permanently or temporarily. Amino acids of these proteins are positioned based on their polarity.
Non-polar amino acids are hydrophobic and are directly integrated into the hydrophobic tails of the phospholipid bilayer.
Contrarily, polar amino acids have hydrophilic domains, and such proteins sit on the surface of the membrane either intracellularly or extracellularly or located internally in such a way that they face aqueous solutions such as in channel proteins.
Types of membrane proteins
Based on the location and nature of membrane-proteins, these proteins are classified as:
- Integral membrane protein
- Peripheral membrane protein, and
- Lipid anchored membrane proteins
Integral Membrane Proteins
- These proteins make up approximately 25% of the human genome
- These are also called transmembrane proteins that span width of the phospholipid bilayer and are permanently anchored to the biological membrane.
- It consists of three segments: Cytoplasmic domain, Exoplasmic domain, and Membrane Spanning Domain.
- The cytoplasmic domain faces towards the cytosolic side, while the exoplasmic domain faces extracellular space. Both the cytosolic and exoplasmic domains interact with the aqueous solutions on the cytosolic and exoplasmic faces of the cell membrane with their hydrophilic exterior surfaces. Amino-acid composition and structure of these domains are similar to that of water-soluble proteins.
- Likewise, the membrane-spanning domain interacts with the hydrophobic hydrocarbon core of the phospholipid bilayer of the membrane with their hydrophobic amino acids side chains protruding out. Thus, they can be removed only by using detergent or non-polar solvents to destroy the membrane structure.
- Transmembrane proteins are amphipathic as these can interact with both hydrophilic and hydrophobic molecules.
- Membrane-spanning domains usually comprise one or more α-helices or multiple β barrels. α-helix bundle proteins are found in all types of biological membranes, but β barrel proteins are found only in the outer membrane of Gram-negative bacteria.
- Moreover, complex branched carbohydrate chains are glycosylated to most membrane proteins of the exoplasmic face.
- These form the part of the entry and exit ways to and from the cell.
- There are several different types of integral membrane proteins:
- Integral monotopic proteins are attached to only one leaflet and do not span across the lipid bilayer,
- Integral bitopic proteins span only once through the lipid bilayer once, and
- Polytopic proteins span more than once through the lipid bilayer.
Peripheral membrane proteins
- These are a class of membrane proteins that attach to biological membranes temporarily.
- They are loosely attached to the membrane through interaction with integral membrane proteins or interaction with the lipid head groups.
- They are named “peripheral proteins” because they do not interact with the hydrophobic core of the bilayer but are instead localized to either the cytosolic or the exoplasmic face of the plasma membrane.
- Moreover, peripheral proteins on the cytosolic face help to form a loose association of cytoskeletal filaments onto lipid bilayer, thereby providing support for cellular membranes. Similarly, peripheral proteins exposed to the exoplasmic surface are attached to extracellular matrix components.
- Most of these proteins are hydrophilic and are associated with ion channels and transmembrane receptors.
- These proteins can be removed by changes in pH or salt content.
Lipid anchored proteins
- They are also known as lipid-linked proteins.
- These proteins are covalently linked to lipid molecule(s) through reversible or irreversible association.
- These can anchor to either leaflet of the membrane lipid and thus are found to localize on either side of the cell membrane.
- Proteins themselves are not embedded; instead, hydrocarbon chains of attached lipids on one leaflet, such as prenyl group anchor proteins through covalent interactions such as thioester bond, amide linkage, etc., or through oligosaccharide linkers such as GPI anchor.
Functions of membrane protein
Different functions associated with membrane proteins are as follow:
Junctions: Membrane proteins connect and join two cells together. Thus, these allow tight junctions to be formed between cells.
Enzymes: Membrane proteins serve as enzymes or biocatalysts to promote chemical reactions. These induce signal transduction process in cells by catalyzing the phosphorylation of the next protein. These also catalyze other types of reactions, such as redox reactions, hydrolytic reactions, and metabolic reactions.
Transport: Membrane proteins form channels or pores as well as act as the transporter, which helps in the movement of nutrients, ions, and other molecules across the membrane. This transport can either be active transport or passive transport.
Cell-cell recognition: Membrane proteins act as recognition molecules as these proteins on the surface of the membrane behave as name tags, which provide information to other cells about the type of cell and its identity. These enable the immune system to distinguish self-cells from foreign cells and selectively attack later.
Anchorage: Membrane proteins are the points of attachment of the internal cytoskeleton to other cells or the extracellular matrix to hold cells in their location.
Signal transduction: Message carried by the extracellular signaling molecule when bound with the receptor membrane protein on the cell membrane activates those proteins. They cause activation of proteins inside the cell, which leads to a signaling cascade resulting change in cell structure or behavior.
- Lodish, H., Berk, A., Kaiser, C. A., Krieger, M., Bretscher, A., Ploegh, H., Martin, K. C., Yaffe, M., & Amon, A. (2021). Molecular Cell Biology (842581) (Ninth ed.). W. H. Freeman.