Lecture 3 Flashcards
Where are all membrane and secretory proteins made?
ER
For proteins to reach their final destination, they must:
Have the correct structure- protein folding
Get to the right place- protein sorting
How are proteins sorted to the correct destination?
Golgi plays a major role in protein sorting
Endoplasmic reticulum
Membrane limited
Flattened sacs: cisternae
Cells that make lots of person have a lot of rough ER
They stain blue (basophilic) due to abundant mRNA
How do proteins get to the ER?
The signal hypothesis
Membrane and secretory proteins have signal sequences at their start
Signal sequence is bound by signal recognition particle (SRP)
SRO directs polysomes (mRNA and ribosomes) to the ER
The protein is extruded into the ER via a channel
The protein is in the ER, now what?
Primary protein structure
Secondary
Three dimensional
Quaternary
The protein folding problem
If you produce a small protein in the test tube, it will fold into its final and correct formation.however for larger proteins, folding is slowe and inefficient.
Why is ER better for protein folding?
Molecular chaperones that bind to nascent proteins and prevent them from aggregating giving them a chance to fold l. Chaperones bind to hydrophobic parts and keep the proteins soluble. They bind with low affinity
Addition of N linked sugars– glycosylation– hydrophilic
Enzymes that catalyze disulfide bond formation disulfide isomerase
Sometimes proteins do not fold correctly because
Hypoxia- folding needs energy Glucose deprivation Aberrations in calcium regulation Viral infection Cancers Mutations
Diseases linked to misfolding
Cystic fibrosis
Hereditary emphysema
Osteogenesis imperfecta
Parkinson’s
If a protein misfolds, what happens?
Loss of function- the cell no longer has the protein. CF
Gain of function ; misfolded protei. Aggregates and causes cell death Alzheimer’s Parkinson’s
Osteogenesis imperfecta
Mutations in type I collagen cause it to misfold;
Misfolded collage. Can be:
Degraded by the cell
Form insoluble aggregates
If not that badly folded, can still be secreted but does not form triple helix normally
