11b channels.2015 - Chapters 11b membrane bound channels...

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Chapters 11b membrane bound channels
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channels are integral membrane proteins / 1000s known essential for controlling diffusion flow the gradients that channels use often set up by carriers/pumps solute flow rapid ~10 6-9 molecules/sec when open each cell has unique combinations of channels majority must be controlled by either external or internal effectors so most are gated in some fashion cell controls them by – electrical potential is modulated / mechanical manipulation of membrane / regulatory ligands / covalent modifications like P / etc. ~11 very large families many traceable to prokaryote’s S 5 S 6 , others not some names indicate what gets moved, while other names imply regulation type most have various but similar isoforms emphasizing importance of gene duplication events and divergence and/or alternative splicing Have generic parts Trans-membrane helixes called S [spanning] or M [membrane ], and the Pore permeability piece [P loop containing selectivity filter and P helix] 2
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3 cycles between 3 states/forms closed – channel closes, then gate moves out of way - nothing gets by – ready to be opened again when open - things pass nearly at diffusion rates – selectivity filter decides what gets by inactivated – something [itself when gated, another ion] impedes flow by blockage switch between pass/no pass is called gating and appears to be all or nothing
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Channel activity total ion flux is determined by # of channels open o some channels spontaneously fluctuate between states o others are gated - require opening – dependent on physiology [binding to regulator, modification] time each channel stays open – o all are designed to open but close – usually fairly quickly o period of open can be modulated by regulators how selective a channel is depends on diameter of pore and whether solute passes as dehydrated [very select] o ion would bind “selectivity loop” nearly as well as water [no energy need] – smallish gap o rate is somewhat limited by ability to bind to narrow slot, 10 6 -10 8 ions/sec o may file across channel single file – repulsion would spit hydrated molecule [less selective] o bigger channels are specific to class of cation / anion GAP pores o let just about anything pass smaller than 800daltons – fastest – think open door 4
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Channel structure and evolution simplest bacterial channels have single peptide/helix that forms a multimer [tetramers common] to produce channel gramicidin [just 13aa], alamethicin and colicins > all peptides used to kill competing bacteria – all K more complex channels evolved with greater # of spanning helixes [2 or more] – although larger, they still group as a multimer to form f[n] channel gene duplication and divergence has yielded many versions First came the S5/S6 coding area which could be duplicated to make families of channels with 2-24 segments An external facing P helix & loop
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