Membrane Proteins

Half of every plasma membrane by mass is protein. Proteins do most of the work: transport, signaling, catalysis, structural anchoring. They sit in the membrane in specific ways depending on their structure.

Integral vs. Peripheral

• Integral membrane proteins: embedded in the bilayer, held there by hydrophobic amino acid interactions with the lipid tails. They can only be removed by disrupting the membrane (detergents). Most span the entire membrane (transmembrane proteins).
• Peripheral membrane proteins: stuck to the surface via interactions with integral proteins or with lipid head groups. They can be removed by mild treatments (salt washes, pH changes) without disrupting the membrane.

Transmembrane Structure

A transmembrane protein crosses the bilayer through one or more membrane-spanning segments. Two common structural motifs:

• Alpha helices: the most common transmembrane motif. A 20-residue hydrophobic alpha helix is long enough to span the 30 Å hydrophobic core of the bilayer. Examples: most receptors, channels, transporters.
• Beta barrels: stacks of antiparallel beta strands form a cylindrical pore. Rare in the plasma membrane but common in the outer membranes of bacteria, mitochondria, and chloroplasts. Example: porins.

Lipid-Anchored Proteins

Some proteins that are not transmembrane nonetheless attach to the membrane via a covalent lipid modification. Examples include:

• GPI anchor (glycosylphosphatidylinositol): links the protein’s C-terminus to the outer leaflet via a GPI moiety. Prion protein (PrP) is GPI-anchored.
• Myristoylation: 14-carbon myristate attached to the N-terminal glycine. Signaling kinases like Src.
• Palmitoylation: 16-carbon palmitate attached to cysteine. Reversible and regulatory.
• Prenylation: attachment of a farnesyl (15C) or geranylgeranyl (20C) isoprenoid. Small GTPases like Ras.

Four Functional Classes

1. Transporters and channels: move molecules across the membrane. Covered in the next sections.
2. Receptors: bind extracellular signals and transmit them inside (GPCRs, RTKs, ion channel receptors).
3. Enzymes: catalyze reactions at the membrane (adenylyl cyclase, phospholipase C, acetylcholinesterase).
4. Anchors and structural proteins: connect the membrane to the cytoskeleton or extracellular matrix (integrins, cadherins, spectrin-ankyrin network).