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Protein Sorting and Cellular Compartmentalization

Cellular compartments I sorting Organelles Membrane-bound sub-compartments Specialised function > Function requires proteins Nucleus needs nuclear proteins ER needs ER proteins Cellular compartments · All proteins start by being synthesised by ribosomes in the cytosol o Something must tell the protein where to go . There are 3 fundamental ways that proteins move around the cell : 1) transport through nuclear pores (gated) 2) transport across membranes 3) transport by vesicles 1 Translation ribosomes cytosolic (mostly) Proteins transported V as required A roadmap of protein traffic Direction CYTOSOL 1 NUCLEUS PEROXISOMES PLASTIDS MITOCHONDRIA ENDOPLASMIC RETICULUM T GOLGI How do proteins know where to go? In fo LATE ENDOSOME LYSOSOMES EARLY ENDOSOME SECRETORY VESICLES r m a ti o CELL SURFACE n KEY: = gated transport = transmembrane transport - = vesicular transport about the destination is encoded in protein sequence (depends on amino acid sequence) V sorting signal = address Most proteins lack sorting signal so will remain in cytosol Others have more than one signal sequence mitochondria, peroxisomes V ER (-> golgi -> other destinations) Cellular compartments · Topological relationship between different compartments · A blue (grey in diagram) dye is inserted into Extracellular space lumen of ER lumen of Golgi lumen of vesicles perinuclear space Cytosol = inside nucleus plasma membrane lysosome rough ER secretory vesicle nucleus inner nuclear membrane envelope outer membrane Golgi endosome apparatus the cell. It fills the cytosol but also stains the nucleus which means that these two things are topologically equivalent . We can also see that the extracellular space is equivalent to the lumen of the different endosomes as well as the perinuclear space Signal sequences 1 Amino acid sequence V adds address to protein > If there is a signal it must be recognised by complementary receptor > Signal sequences can be located anywhere on the protein (can be at the N-terminus or c-terminus , they can be in the middle of the protein, they can be in one patch etc) If located at one of the end termini then often the signal sequence will be cleaved off V But if distributed in smaller patches throughout the unfolded protein, when it folds they will form a signal patch that will be recognised by the receptor. Continuous or discontinuous > Can be removed after sorting by enzymes V signal may not be part of final protein signal sequence UNFOLDED PROTEIN FOLDED PROTEIN COOH H2N COOH NH2 signal sequence (A) H2N COOH HA2N signal patch COOH regions contributing to signal patch . If you want to import protein into the nucleus the signal sequence can be anywhere in the protein sequence, but a characteristic feature is that there will be a stretch of very positively charged amino acids. . If we want to export from the nucleus, the signal sequence can be anywhere but will be rich in hydrophobic amino acids. · Mitochondria and plastids have very long and complicated signal sequences but the ss will be located at the very end terminus