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That proteins which enter the secretory pathway have

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Unformatted text preview: 12 9/14/2013 The signal hypothesis states that proteins which enter the secretory pathway have sequence of amino acids at their N-terminus that directs the nascent polypeptide to the ER, and guides the polypeptide during translation into the lumen of the ER. This sequence of amino acids is known as the signal sequence or signal peptide. 13 9/14/2013 Insertion of the signal sequence through the membrane requires GTP hydrolysis. The signal recognition protein (SRP) and the SRP receptor both bind and hydrolyze GTP to power the conformational changes that open the translocon and insert the signal sequence into the translocon. translocon- pore forming protein in the membrane translocon will allow for opening upon cleavage of GDP BP- chaperone that allows for polypeptide to fold correctly as its entering the lumen 14 9/14/2013 if signal sequence isn't cleaved it will embed in plasma membrane instead of being secreted 15 9/14/2013 Pulse Chase Experiments helped define the secretory pathway: after 5 minutesblack dots (indicating isotope) will be in the rough ER 20 minutes laterblack dots are in the golgi apparatus for the most part 40 minutes latermost are in the transport vesicles of golgi 80 minutes- label associated with proteins outside the cell if looked at an integral instead might see a lot in plasma membrane after 80 minutes 16 9/14/2013 17 9/14/2013 Some typical signal sequences: target proteins to different parts of the cellconsensus sequences- might not be exact as below but appear most frequently Import into ER: +H3N-Met -Met-Ser-Phe-Val-Ser-Leu-Leu-Leu-Val-Gly-Ile-LeuPhe-Try-Ala-Thr-Glu-Ala-Glu-Gln-Leu-Thr-Lys-Cys-Glu-Val-Phe-GlnRetain in ER: -Lys-Asp-Glu-Leu--COO- < signal peptide: roughly 20 a.a.'s at terminus < car boxy terminus end Import into nucleus: -Pro-Pro-Lys-Lys-Lys-Arg-Lys-ValExport from nucleus: -Leu-Ala-Leu-Lys-Leu-Ala-Gly-Leu-Asp-IleImport into mitochondria: +H3N-Met-Leu-Ser-Leu-Arg-Gln-Ser-Ile-ArgPhe-Phe-Lys-Pro-Ala-Thr-Arg-Thr-Leu-Cys-Ser-Ser-Arg-Tyr-Leu-LeuImport into peroxisomes: -Ser-Lys-Leu-COO- 18 9/14/2013 19 9/14/2013 The role of phospholipid translocators in lipid bilayer synthesis phospholipid translocators = Scramblase (ABC transporter Family) 20...
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