Lecture 2

• Membrane proteins and transport across membranes are the focus of this lecture
• The lecture will discuss the permeability of the lipid bilayer, passive and active transport, classes of membrane transport proteins (channel proteins, transporters, uniporters, sorters, antiporters), and ATP-driven pumps
• Membrane transport is essential for life and is important in various diseases, with cystic fibrosis as a common example
• Cystic fibrosis


  A recessive genetic disease that causes progressive disability and early death, with the most common symptom being difficulty breathing due to frequent lung infections
• CFTR gene


  Often mutated in cystic fibrosis, the CFTR protein is required to regulate the components of sweat, digestive juices, and mucus
• CFTR protein


  An ABC transporter class transporter protein that transports chloride and thiocyanate
• CFTR protein not working

  Water does not follow properly by osmosis, leading to issues with the consistency of mucus
• Artificial lipid bilayer


  Permeable to small non-polar and uncharged polar molecules, but impermeable to large uncharged polar molecules and ions
• Simple diffusion


  Movement of molecules from high concentration to low concentration through the lipid bilayer
• Membrane transport proteins


  Create a protein-lined path across the cell membrane to transport polar and charged molecules like ions, sugars, amino acids, nucleotides, and cell metabolites
• Channel proteins


  Bind weakly to the transported molecule and do not change in confirmation a lot during transport
• Transporter proteins (carrier proteins)


  Bind strongly to the transported molecule and do change in confirmation a lot during transport
• Channel proteins


  • Selectivity based on size and electric charge of the solute, transient interactions as the solute passes through, generally no or little conformational changes
• Transporter proteins


  • Solute fits into the binding site, specific binding of the solute, series of conformational changes for transport
• Passive transport


  Down or with the concentration gradient, does not directly require energy
• Active transport


  Against or up the concentration gradient, does directly require energy
• Membrane transport proteins


  • Channel proteins
  • Transporter proteins (including pumps)
• Concentration gradient


  Direction of the gradient, not necessarily the direction of transport
• Channel proteins do passive transport, some transporter proteins do passive, some do active transport
• Concentration gradient


  Difference in concentration of a substance across a membrane
• Passive transport


  Transport down or with the concentration gradient, does not directly require energy
• Active transport


  Transport up or against the concentration gradient, does directly require energy
• Channels


  Proteins that facilitate passive transport
• Transporters


  Proteins that can facilitate both passive and active transport
• Electrochemical gradient


  Combination of the concentration gradient and the electrical gradient (membrane potential)
• Typically in the cell, the concentration difference is a bit stronger and tends to win out over the electrical gradient
• Transport proteins


  • Can be channels (passive) or transporters (passive and active)
• Channel proteins


  Have a hydrophilic pore across the membrane, allow passive transport, are often selective for specific ions
• Non-gated ion channels


  • Potassium leak channel
• Non-gated ion channels


  Always open, allow constant flow down concentration gradient
• Gated ion channels


  Require a signal to open, can be mechanically gated, ligand-gated, or voltage-gated
• Mechanically gated ion channels

  • Stretch receptors, hearing receptors
• Voltage-gated ion channels


  • Open in response to changes in membrane potential
• Gated intracellular ligand signal could be an ion or a nucleotide
• The signal is a change in voltage across the membrane
• Membrane depolarization can cause the protein to change conformation and open up
• Transporters


  Bind a specific solute and go through a conformational change to transport the solute across the membrane
• Transporter proteins


  • Bind to the blue molecule
  • The shape changes a lot
• For channel proteins, the more of the molecule on one side of the membrane


  The faster the transport
• For passive transporters, the more of the molecule on one side


  The faster the transport, but they eventually max out