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PROTEINS AND MEMBRANES

PROTEINS AND MEMBRANES. Proteins: Recall protein secondary structures:  -helices and ß-sheets. Proteins in membranes. Proteins in membranes. Bacteriorhodopsin: note the seven membrane-spanning  -helices. Maltoporin: a ß-barrel protein, with membrane-spanning ß sheets.

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PROTEINS AND MEMBRANES

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  1. PROTEINS AND MEMBRANES

  2. Proteins: Recall protein secondary structures: -helices and ß-sheets

  3. Proteins in membranes

  4. Proteins in membranes

  5. Bacteriorhodopsin: note the seven membrane-spanning -helices

  6. Maltoporin: a ß-barrel protein, with membrane-spanning ß sheets

  7. Although they are not common, there are several ß-barrel proteins known-- primarily trans-membrane transport proteins.

  8. Unilateral membrane embedding may occur through hydrophobic amino acids Or connection to glycolipids

  9. Folding of membrane protein during synthesis is complex: Folding of lactose permease depends on the lipid composition of the membrane. Folding of aquaporin involves changes in the orientation of alpha- helices. (Science 339:398, 25 January 2013)

  10. Membranes are heterogeneous: Membrane “rafts” are accumulations of proteins, stabilized by glycosphingolipids and cholesterol. (Science 327:46, 1 January 2010)

  11. The purpose of membranes is to control transport into and out of the cell or from one cell compartment to another.

  12. Example of a channel: A nerve impulse involves depolarization, followed by re-polarization. Nerve cells’ electrical polarity results from coupled Na+ efflux and K+ influx. Depolarization results from Na+ influx (opened Na+ channels). Re-polarization results from K+ efflux (opened K+ channels).

  13. Potassium channel: responsible for re-polarizing nerve cells after a nerve impulse. Note the 3-angstrom constriction with negatively charged groups. How does this channel control K+ movement, and why is it specific for K+?

  14. This is the slide used to explain the ability of enzymes to catalyze chemical reactions: does this apply to the operation of channels? Enzymes bind to substrates, so G(ES) < G(E+S). However, if all they did was to bind, then G for the reaction would not be reduced. So when they bind the substrate, they stress It in some way, raising G(ES) and reducing G(ES*)(=Ea).

  15. The specificity of the K+ channel for K+, relative to Na+, depends on desolvation and resolvation energy. What would explain the specificity of the Na+ channel?

  16. From Science, 3/12/2010: “Pain’s in the genes”: “Subtle changes to a certain gene seem to determine how sensitive people are to pain, according to new research. In the past 5 years, researchers have discovered that three rare but serious pain disorders are caused by mutations in a gene called SCN9A. In nerve cells that relay painful sensations in the body's tissues to the central nervous system,…” How many of you are particularly sensitive to pain? …particularly insensitive? What do you think the mutation affected? (a) A membrane lipid (b) A channel (c) A carrier (d) A pump

  17. Mechanosensitive channels in bacteria: these open in response to high tension (Science 321:1166, 29 August 2008)

  18. Summary • Intrinsic membrane proteins generally cross the membrane • with an -helix • Some membrane pore proteins use a ß-barrel structure • Membrane proteins can associate in “rafts” stabilized by • sterols and sphingolipids • Hydrophilic molecules, including ions, cross membranes through • channels and pumps • Nerve function (and other functions) depend on control of • channel opening • The specificity of the potassium channel depends on solvation- • desolvation energy • Mutations in channel proteins influence ease of nerve • stimulation

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