LS1a_L18_notes08_part1

LS1a_L18_notes08_part1 - LIFE SCIENCE 1a S PROF. ROBERT LUE...

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PROF. ROBERT LUE NOVEMBER 18, 2008 1a L I F E S C I E N C E S 1
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Protein targeting 1. The sorting of proteins to specific subcellular domains - Signal sequences target proteins to their cellular destinations - Secreted proteins, transmembrane proteins, and some organelle proteins must first enter the ER - Vesicle transport moves both proteins and membranes - SNARE proteins define the specificity of vesicle targeting 2
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coat protein SNARE proteins target vesicles to specific destinations v-SNAREs on vesicles dock with t-SNAREs on specific target membranes Targeting depends on the match between a particular v-SNARE and t-SNARE Vesicles have to recognize the correct target membrane; because there are many membranes, a vesicle is likely to encounter many potential targets. Proteins called SNAREs (which stands for Golgi SNAP receptor complex protein, a name that is not important for this course) are thought to play a role in determining which vesicles fuse with which compartments. SpeciFcity in targeting is ensured because vesicles display v-SNAREs (vesicle SNAREs) on their surface that identify them according to their origin and type of cargo; target membranes display complementary t-SNAREs (target SNAREs) that recognize the v-SNAREs. ±or example, in this picture the pink v-SNARE pairs with the light blue t-SNARE on compartment A, targeting cargo a to compartment A. Similarly, the red v-SNARE on vesicles containing cargo b binds to the bright blue t-SNARE on compartment B. This diagram also shows the cargo receptor (brown) and vesicle coat (green); we previously discussed how the coat proteins play a role in deforming the membrane to form a vesicle and in helping to select cargo for inclusion in the vesicle. Cargo selection is achieved indirectly - the coat protein interacts with a cargo receptor, which in turn binds to cargo proteins (yellow) that are to be included in the vesicle. These interactions ensure that the correct cargo is selected for inclusion in the vesicle. In addition, the protein coat depolymerizes with the help of other regulatory proteins before the vesicle can fuse with the target membrane. Once the vesicle has formed with the speciFed cargo, the protein coat has no further function and would get in the way of SNARE to SNARE binding if it were not removed by depolymerization. 3
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Stalk formation vesicle target v-SNARE t-SNARE Hemi-fusion Fusion Squeeze out water molecules SNARE proteins facilitate membrane fusion In addition to their role in targeting vesicles to the correct target compartments, SNAREs are thought to play a role in membrane fusion. SpeciFcally, the highly favorable interactions between the v- and t-SNAREs is used to overcome the unfavorable electrostatic repulsion that occurs when the two cell membranes are brought together. v-SNAREs pair with t-SNAREs to form a very stable bundle of four alpha-helices that forces the two membranes into
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LS1a_L18_notes08_part1 - LIFE SCIENCE 1a S PROF. ROBERT LUE...

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