Ch_10_Protein_Sorting

Ch_10_Protein_Sorting - Endoplasmic Reticulum Largest...

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Endoplasmic Reticulum Largest organelle of most eukaryotic cells Lumen/cisternal space is 10% of cell volume. Rough ER is covered by ribosomes Secretory pathway: 1. Rough ER 2. Goli 3. Secretory vesicles 4. Cell exterior Cotranslational translocation- proteins translated to ER during synthesis on membrane bound ribosomes. o Ribosomes targeted to ER membrane by AA sequence of polypeptide chain. o Signal sequence at amino terminus of growing chain recognized. Short stretches of hydrophobic AA. Posttranslational translocation- proteins translocated to ER after translation has been completed on free ribosomes in cytosol. Signal sequences- Cotranslational translocation Target ribosomes to ER membrane (translocons aka Sec 61 proteins) Hydrophobic part spans 20-30 AA (entire is 35-40 AA). Recognized and bound by Signal Recognition Particle (SRP) as they emerge from the ribosome. o SRP consists of 6 polypeptides and a small cytoplasmic RNA (srpRNA) Small binds ribosome, inhibits translation o SRP binds ribosome AND signal sequence, stopping translation. o Targets entire complex to rough ER, binds to SRP receptor on the ER membrane. o GTP hydrolysis dissociates SRP from complex, translation continues in ER. o Signal peptidase cleaves signal seq. Posttranslational translocation Free ribosome synthezes protein which is released to cytosol. Then can be sent to ER, nucleus, or mitochondria. Chaperones take protein to ER, keep protein linearized so it can pass thru translocon (aka Sec62/63) NOTE: There is still a signal sequence BiP- HSP70 chaperone, ER resident protein binds ATP and grabs and ratchets the protein in o Many BiP’s needed for PTT. Membrane proteins Internal signal sequence- orientation of signal determines orientation of protein. Lumen is topologically equivalent to outside of cell.
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Proteins are synthesized the same way they will be secreted. Have hydrophobic 20-25 AA alpha helix regions spanning membrane. Stop-transfer sequences cause sequence to be stuck in membrane, translation continues in cytosol. Start-transfer, translation continues in lumen.
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This note was uploaded on 03/19/2008 for the course MMG 409 taught by Professor Arvidson during the Spring '08 term at Michigan State University.

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Ch_10_Protein_Sorting - Endoplasmic Reticulum Largest...

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