Chapter 10 since we left off on the last test VII Porins maltoporin specifically transports the sugar maltodextran helical greasy slide through center of channel centerofchannellinedwithhydrophobicresidues edgeshavepolargroups a polars interact with OH of sugar b nonpolar interact with C in center of sugar VIII Ion channels big difference with porins and ionophores is that they can be regulated turned on off in Transmembrane always passive ion channels allows the flowing down the concentration gradient A common characteristics 1 selectivity filter a a that bind specifically to substrate 2 aqueous cavity vestibule or funnels that restrict dimensions of pore 3 selectivity filter often binds multiple copies of substrate at once 4 presence of a gate that responds to some triggering signal IX Most cells maintain concentration gradient of K Na and Cl for mammals 1 extracellular 150mMNa 4mMK 120mMCl 2 intracellular 12mMNa 140mMK 4mMCl opening and closing of ion channels function in signaling regulation of osmolarity nerve impulses X K channel example diffuse from cytoplasm to extracellular space Rod MacKinnon nobel prize in 03 for work on struct func of ion channels KcsA pH gated K channel in bacteria a opens in response to low intracellular pH in bacteria Lots of K on the inside need to neutralize by pumping K out b helps maintain osmolarity also involved in cell signaling C4tetramer four inner helices which largely form the pore pack against each other near the cytoplasmic side of the membrane much like poles of an inverted teepee The four outer helices which face the lipid bilayer buttress the inner helices The central pore can accommodate several K ions 10 000X more permeable to K than Na XI specificity mediated by selectivity filter a extremely narrow pore in center of molecule b pore has variable width at cytoplasmic side have entrance lined with four anionic side chains that attract cations and repel anions c the pore than widens so that K ions can move through in its hydrated state d however upper part of the pore the selectivity filter narrows therefore forcing a transiting K ion to shed its waters of hydration b dehydrates K by substituting coord with H2O with coord to backbone carbonyl c binds 4K but not all at once 1 if all 4 in filter at same time would repel each other 2 alternates K H2O K H2O selective for K over Na despite small difference in radius 1 33 for K vs 95 for Na The structure of the protein surrounding the selectivity filter suggests that the diameter of the pore is rigidly maintained thus making the energy of a dehydrated Na in the selectivity filter considerably higher than that of hydrated Na and thereby accounting for the K channel s high selectivity for K ions openstate closedstate gated by pH Figure 10 5 shows a string of regularly spaced K ions four in the selectivity filter and two more just outside it on its extracellular top side Such closely spaced positive ions would strongly repel one another and hence represent a high energy situation However the X ray structure is an average of many KcsA molecules and a variety of evidence indicates that within a single channel the K ions in the pore actually alternate with water molecules This arrangement means that each K ion is surrounded by O atoms from H2O or protein carbonyl groups at each position along the selectivity filter As a K ion moves into the selectivity filter from the cavity it exchanges some of its hydrating water molecules for protein ligands then does the reverse to restore its hydration shell when it exits the selectivity filter to enter the extracellular solution Set up so when the K ion moves through the filter there is little free energy change which allows for rapid movement of K ions through the ion channel Many types of gated ion channels Mechanosensitive opened by deformation of bilayer respond to direct physical stimuli such as touch sound changes in osmotic pressure Ligand gated opened by binding of ligand like neurotransmitter nerves synapses Signal gated opened intracellularly by binding by signal molecule like Ca2 Voltage gated opened by change in membrane potential 1 Very important in nerve impulses 2 action potentials XII Action potential Wave of transient depolarization that propagates down length of nerve cell mediated by opening and closing of Na and K channels Higher Na outside the cell Higher K inside cell Resting membrane potential 60mV Stimulus leads to spontaneous opening of Na channel a Na rush in depolarization 1 induces opening of neighboring Na channels propagation of signal b induces opening of K channels 1 K rush out repolarization a hyperpolarization When K rushes out induces closing of channel Action potential is directional b c once channel opens there is a delay before in can open again Before the distribution of Na and K ions across the membrane equilibratesm the Na and K channels spontaneously close and remain closed until the membrane potential has regained its resting value As AP is propagated along the length of a nerve cell it is continuously renewed so that its signal strength remains constant In contrast to electrical impulses XIII K channel in nerves called Kv Voltage gated K channel Kv channels have two gates 1 S4 helix acts as voltage sensor a Has series of 4 charged Arg residues b Moves in response to membrane potential when membrane potential increases the inside becomes less negative the S4 helix is pulled toward the extracellular side of the membrane 1 Leads to conformational change from closed conformation to open conformation enlarge the intracellular entrance to the K channel Senses depolarization 2 2nd gate mediates closing during hyperpolarization mediated by inactivation ball that blocks opening of channel the ball swings around to the bind in the mouth of the open K pore thereby blocking the passage of K ions XIV Aquaporins Transport H2O across membrane at very fast rate but do not permit transport of solutes or ions 1 important in tear production absorption of water in kidney salivary glands very specific even selective against H3O 2 important b c transport of H3O would depolarize membrane C Structure Tetrameric 1 Each monomer form a pore unlike Mb a Pore contains constriction at center 2 Specifically orients water so that H bond network is broken therefore can t form water wire that would depolarize membrane XV some transporters do not form a pore A non channel transporters 1 Conformational change mediates transport of substrate 2