Lecture 5: Mitochondrial & ER Protein Transport

T or F with non pore transport (ER & Mito) the proteins are unfolded and “un-mature” also they are kept this way by chaperones

True

The four spaces of the mitochondria

outer-memebrane, intermebrane space, inner-membrane, matrix

Mitochondrial Matrix

the straight up inside of the mitochondria, past both membranes and the inter membrane space

The process of proteins getting into the Mitochondria 

1. You have a fully translated protein held unfolded by hyperons that has a signal sequence

2. The signal sequence is recognized by the Import Receptor Protein and grabbed

3. Import Receptor Protein hands the protein off to TOM

4. TOM transports it through the outer membrane and hands it off to TIM

5. The signal sequence enters the intermemebrane space where TIM recognizes it and chaperons help it stay unfolded

6. TOM & TIM help get the protein through

7. The chaperones leave and the protein matures, then the signal sequence is cleaved

Import Receptor Protein

protein that lies on the surface of the outer-membrane of the mitochrondria that receives the proteins with the signal sequences, passing it off to TOM. 

TOM (Translocase of the outer mitochondrial membrane)

• protein that is given a protein trying to enter to mitochondria, & helps it get through alongside TIM 

• specific to protein transport into the mitochondria 

TIM (Translocase of the inner mitochondrial space)

• protein that is given a protein trying to enter to mitochondria, & helps it get through alongside TOM 

• specific to protein transport into the mitochondria 

Chaperones

• proteins that help other proteins fold properly OR stay unfolded (un-mature)

• exist and help mitochondrial protein import, both pre and during import

• ATPases that use ATP hydrolysis (binding & unbinding) to power their ability to keep proteins unfolded

T or F Cystolic and mitochondria chaperones are needed for mitochondrial protein import

TRUEEE

Cystolic and mitochondria chaperones function

• cystolic ones keep them unfolded (unmature)

• mitochondrial ones fold and help the protein through (mature)

if a protein is to stay in the intermembrane space what MUST it have?

• a StopTransfer Sequence, that tells the TOM & TIM to stop transferring.

• and a stop transfer sequence that ANCHORS the proton to the inter membrane space

Stop Transfer Sequence

• hydrophobic amino acids sequence that prevents further translocation across membrane

• keep proteins anchored in the intermemebrane space 

Co-translational Import

• protein transport that happens during translation, in particular stopping it for a second

• specific to ER protein transport

Post-Translational Import

import that happens after a protein is made

• examples being NCP transport & Mitochondrial transport

ER Protein transport stepwise 

1. The signal sequence of the protein is made by the ribosome and is IMMEDIATELY recognized  by SRP, halting translation when it binds 

2. The SRP binds to the SRP receptor, the SRP goes home and translation resumes

3. Proteins are made into eh ER lumen, and the signal sequence is cleaved by peptidase

4. the protein pulls through and matures

(more if the protein is integral[think of the 3 ways]/soluble) 

SRP

signal receptor protein, that recognizes signal sequences made ribosome and snags it the second it exists, halting translation and binding to the SRP receptor

SRP Receptor

• receives the protein and once the SRP binds, translation resumes

ER Lumen 

the legit inside of the ER

Peptidase

• protein that cleaves off signal sequences

What is required for ER Protein transport if the protein is integral

Start/Stop Sequences

Start/Stop Sequences

• Sequences that stop and start translocation, resulting in parts of the protein being in the lumen or in the cytosol

• Internal Start/Stop sequences are not cleaved off 

• Become transmembrane domains