Membrane protein
Membrane proteins are common, diverse, and key drug targets.
Membrane proteins are common proteins that are part of, or interact with, biological membranes. They fall into several broad categories depending on their location: integral membrane proteins are a permanent part of a cell membrane, while peripheral membrane proteins are transiently associated with the cell membrane. Membrane proteins are medically important—about a third of all human proteins are membrane proteins, and these are targets for more than half of all drugs.
- field
- Molecular biology, biochemistry
- known_for
- Integral and peripheral membrane proteins, transmembrane proteins, drug targets
- proportion_of_human_proteins
- ~33%
- proportion_of_drug_targets
- >50%
- estimated_genome_encoding_in_humans
- 30%
Lore & Background
Membrane proteins are embedded into membranes through complex pathways. When transmembrane proteins are translated from RNA, they have start-transfer-sequences and stop-transfer-sequences before posttranslational modifications. The start-transfer-sequence recruits a signal recognition particle (SRP), which stops translation until it binds to an SRP-receptor on the lipid bilayer surface. Translocons are channels that allow proteins to be moved across the membrane, and the ribosome synthesizes the polypeptide directly through them. Many other complex pathways for embedding proteins exist, specific to eukaryotes and prokaryotes respectively. Integral membrane proteins are permanently attached to the membrane and can be separated only using detergents, nonpolar solvents, or denaturing agents. They include integral polytopic proteins (spanning the membrane more than once), bitopic proteins (spanning once), and integral monotopic proteins (attached to only one side). Peripheral membrane proteins are temporarily attached via hydrophobic, electrostatic, and other non-covalent interactions, and dissociate following treatment with a polar reagent such as elevated pH or high salt concentrations. Membrane proteins perform vital functions: membrane receptor proteins relay signals between the cell's internal and external environments; transport proteins move molecules and ions across the membrane; membrane enzymes have activities such as oxidoreductase, transferase, or hydrolase; and cell adhesion molecules allow cells to identify each other and interact. The localization of proteins in membranes can be predicted reliably using hydrophobicity analyses of protein sequences.
Reader's Guide
Membrane proteins are significant because they are common and medically important—about a third of all human proteins are membrane proteins, and they are targets for more than half of all drugs. Despite this, determining membrane protein structures remains a challenge due to the difficulty in establishing experimental conditions that preserve the native conformation in isolation from the native environment. Their hydrophobic surfaces make structural and functional characterization difficult. Detergents can render membrane proteins water-soluble but may alter structure and function; engineering the protein sequence by replacing hydrophobic amino acids with hydrophilic ones is another approach. Affinity chromatography, using tags such as polyhistidine or rho1D4, is one of the best solutions for purification. Membrane proteins are implicated in human diseases including heart disease, Alzheimer's, and cystic fibrosis. Polypeptide toxins and certain antibacterial peptides are sometimes considered a separate category; these proteins are water-soluble but can undergo conformational changes and associate with the lipid bilayer.
Did You Know?
- About a third of all human proteins are membrane proteins, and these are targets for more than half of all drugs.
- Integral membrane proteins can be separated from biological membranes only using detergents, nonpolar solvents, or sometimes denaturing agents.
- Membrane proteins have been implicated in heart disease, Alzheimer's, and cystic fibrosis.
Frequently Asked Questions
What is a membrane protein?
A membrane protein is a protein that either sits permanently within a biological membrane or temporarily associates with it. They are a major class of cellular proteins found across virtually every organism.
What are the main types of membrane proteins?
They split into two broad groups: integral membrane proteins, which are permanently embedded in the lipid bilayer, and peripheral membrane proteins, which attach to the membrane surface only transiently. Transmembrane proteins are a well-known subset of the integral category.
Why are membrane proteins such a big deal in medicine?
Roughly one-third of all human proteins are membrane proteins, and more than half of every drug currently in use targets one of them. This makes them the single most important class of molecular drug targets in pharmacology.
How many membrane proteins does the human genome encode?
About 30 percent of all protein-coding genes in the human genome produce membrane proteins, underscoring just how central they are to cell biology.
What's the key difference between integral and peripheral membrane proteins?
Integral proteins are a permanent structural component of the membrane, spanning or deeply embedded in the lipid bilayer. Peripheral proteins, by contrast, bind only loosely and temporarily to the membrane surface, making them far easier to strip away during lab isolation.
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