L17 - Chapter 6 pages 359-366 Chapter 12 pages 704-712 Chapter 19 pages 1131-1144 1150-1154;1165-1172 1178-1194 Ofce hours tomorrow Nuclear Pore

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Chapter 6 pages: 359-366 Chapter 12 pages: 704-712 Chapter 19 pages: 1131-1144; 1150-1154;1165-1172; 1178-1194 • OfFce hours tomorrow.
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Nuclear Pore Generated by Samir Patel in Micheal Rexach’s lab using computer graphics. These are artistic renditions based on all the available data. Part cryo em, part scanning em , part biophysical measurements.
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Regulated Transport through the Nuclear Pore: Nuclear Localization Signals (NLS) Targeting of a protein to the nucleus requires a signal on the protein. What is the signal? The first clue came from studying a virus that infects monkey cells. Simian virus 40 - SV40. A mutant virus was found that could not replicate its DNA. Turned out that the T antigen protein encoded by the virus was mutated and could not get into the nucleus. IMPORTANT POINT: there are both nuclear import and nuclear export signals.
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Nuclear Import/ Export Receptors Bind Nuclear Import Signal and Nuclear Export Signals NLSs have been identified for many different nuclear proteins. Common properties: -signal is internal -typically 4-8 AA long -not cleaved during transport Imported and Exported proteins need these signals to recognize their receptors Sometimes adaptors are used Combined use of different receptors and adaptors allows a cell to recognize many NLSs 1,2,3 all have different NLSs even though each one is depicted as a red circle
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The nuclear import/export receptors bind to the nuclear import or export signal on proteins, and then bind to the fibrils composed of nucleoporins that have FG repeats. Nuclear Import/ Export Receptors also Bind Nucleoporins Nucleoporins that make the fibrils have AA phenylalanine/glycine (FG) repeats These serve as binding sites for nuclear import receptors. FG repeats line the the path through the nuclear pore
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One gene family (called Karyopherins) encodes both nuclear import and nuclear export receptors. It has been shown that a single pore can conduct traffic in both directions, but it is unknown how a pore complex coordinates bidirectional flow of macromolecules to avoid traffic jams and head on collisions. Nuclear Export Receptors bind to nuclear export signals What is known is that a GTPase (called Ran) drives directional transport through the nuclear pore. Nuclear Export Receptors Work in a Similar Fashion only in REVERSE
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The Ran GTPase and its GAP and GEF Ran, like ALL GTPases, exists in 2 conformational forms--bound to GTP and bound to GDP . The gradient of these 2 conformational forms drives nuclear transport in the appropriate direction. These 2 conformational forms are restricted due to the restricted localization of the GTPase regulatory proteins: Ran-GAP is located in the cytosol & Ran-GEF is located in the nucleus bound to chromati n
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Ran-GTP controls access to a conserved region on the nuclear import receptor that is important for NLS binding This is co-crystal of nuclear IMPORT receptor. Nuclear transport receptor actually look like those squiggly lines in the artist’s picture! They are composed of repeated
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This note was uploaded on 03/28/2010 for the course MCD BIO 110 taught by Professor Hinck during the Fall '09 term at University of California, Santa Cruz.

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L17 - Chapter 6 pages 359-366 Chapter 12 pages 704-712 Chapter 19 pages 1131-1144 1150-1154;1165-1172 1178-1194 Ofce hours tomorrow Nuclear Pore

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