12.11
Multi-pass Transmembrane Proteins and β-barrels
In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α…
In multi-pass membrane proteins, the interaction between multiple transmembrane domains determines their structure and function.
G protein-coupled receptors are the largest family of membrane proteins. They contain seven transmembrane alpha-helices which act to transmit signals between the cell's extracellular and intracellular environments.
In contrast, many channel-forming membrane proteins, such as porins, contain multiple beta-strands of the protein. These form hydrogen bonds to form a continuous cylindrical beta-sheet, creating a rigid ring-like structure called a beta-barrel.
The amino acids in the strands alternate between polar and non-polar residues. Non-polar groups point towards the outside of the barrel and interact with the hydrophobic membrane.
The polar side chains orient towards the inner hydrophilic opening, which forms a channel from the extracellular to intracellular space allowing the passage of small polar solutes.
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Q1: What are the main structural differences between G protein-coupled receptors and porins?
G protein-coupled receptors contain seven transmembrane alpha-helices that transmit signals between extracellular and intracellular environments. Porins, in contrast, use multiple beta-strands arranged into a rigid ring-like beta-barrel structure. While GPCRs facilitate cell signaling, porins form channels allowing passage of small polar solutes across membranes.
Q2: How do beta-barrel structures form in porin proteins?
Beta-strands in porins arrange into a cylindrical ring-like structure where edges of closely spaced strands form hydrogen bonds together. A minimum of eight beta-strands are required to create the barrel. The alternating polar and non-polar amino acids orient strategically: non-polar residues face outward toward the hydrophobic membrane, while polar side chains point inward toward the hydrophilic channel opening.
Q3: Why do multi-pass transmembrane proteins use different secondary structures?
Alpha-helix containing multi-pass transmembrane proteins like GPCRs are ubiquitous across cell types and organisms. Beta-strand containing proteins are mainly found in gram-negative bacteria, mitochondria, and chloroplasts. This distribution suggests that mitochondria and chloroplasts evolved from prokaryotes, as they retain the beta-barrel porin architecture characteristic of bacterial membranes.
Q4: What role do polar and non-polar amino acids play in beta-barrel channel function?
In beta-barrel structures, amino acids alternate between polar and non-polar residues. Non-polar groups point outward and interact with the hydrophobic membrane lipids, anchoring the protein. Polar side chains orient inward, creating a hydrophilic channel opening that allows small polar solutes to pass from the extracellular to intracellular space.
Q5: How do G protein-coupled receptors transmit signals across the membrane?
All GPCRs have seven transmembrane alpha-helices, though each receptor has specific extracellular domains and G-protein-binding sites. When a ligand binds to the receptor, it activates a membrane protein called G-protein. The activated G-protein then interacts with either an ion channel or an enzyme in the membrane to propagate the signal.
Q6: What is bacteriorhodopsin and how does it function in bacterial membranes?
Bacteriorhodopsin is a light-driven proton pump found in certain photosynthetic bacteria with seven transmembrane alpha-helices. It generates a proton gradient across the membrane using light energy, which drives ATP production. This mechanism demonstrates how multi-pass transmembrane proteins can harness energy for cellular processes beyond signal transduction.
Q7: Where are porin proteins found and what does their distribution reveal about cell evolution?
Porin proteins containing transmembrane beta-barrels are observed in gram-negative bacterial membranes and also in mitochondrial and chloroplast membranes. Their presence in mitochondria and chloroplasts supports the endosymbiotic hypothesis that these organelles evolved from prokaryotes, as they retain the characteristic beta-barrel architecture of bacterial membrane proteins.