Week 10 (Cellular Compartments I Sorting) Flashcards
How do proteins know where to go?
➢Destination depends on amino acid sequence
•sorting signal =address
➢Most proteins lack sorting signal
•remain in cytosol
➢Others have more than one signal sequence
• mitochondria, peroxisomes
•ER (→ golgi → other destinations)
Topological relationship: what is the ECS topologically equivalent to?
Extracellular space is topologically equivalent to: lumen of ER lumen of Golgi lumen of vesicles perinuclear space
Cytosol = inside nucleus
What is the function of Signal Sequences
➢Amino acid sequence •adds address to protein ➢Recognised by receptor proteins (complementary) ➢Continuous or discontinuous ➢Can be removed after sorting by enzymes •signal may not be part of final protein
What are the 3 mechanisms to move protein from one compartment to another?
- Gated transport
- Transmembrane transport
- Vesicular transport
Explain Gated Transport
➢Movement between topologically equivalent spaces
•No need to cross membranes
➢Cytosol ↔ nucleus
➢Guided by signal sequences
➢Signal sequence recognised by receptor protein guides protein across nuclear pore complex
➢bidirectional movement
•e.g. ribosomal subunits
Gated Transport: explain the action of nuclear import/export proteins
➢Nuclear pore complexes (NPCs)
•over 30 proteins “nucleoporins”
➢Nuclear Import Receptors
•soluble cytosolic proteins
•recognise nuclear localisation sequences (signal sequence directing protein to nucleus)
•deliver proteins to nuclear pore for transport
➢To transport out of nucleus = reverse
•nuclear export signal sequence
•nuclear export receptors
Transport across nuclear membrane: size cut off
- Small molecules (<60kDa) can diffuse through the gates
- Large molecules need active transport
- DNA/RNA polymerases (100-200kDa)
- Ribosomal subunits (30nm)
Transport across nuclear membrane: nuclear import receptors
➢Soluble Nuclear import receptors (importins) recognise and bind to nuclear localisation signal (NLS) and they bind nuclear pore complex proteins and they guide movement of proteins through the gates
➢Soluble Nuclear export receptors (exportins)
➢Nuclear export works like nuclear import, but in reverse
Describe Transmembrane Transport
➢Transports across membranes ➢Membrane-bound translocators ➢Unfolded proteins snake through translocators ➢Cytosol → mitochondria ➢Cytosol → ER
Endoplasmic Reticulum
➢Rough ER: coated with ribosomes
➢Membrane separates lumen from cytosol
➢Captures proteins from the cytosol during synthesis
ER: Soluble proteins
- transported fully across the membrane
* destined for secretion or to be inside other organelle
ER: Transmembrane proteins,
- partly transferred across the membrane
- remain embedded in membrane
- destined to reside in a cellular membrane
How are proteins transported into ER
➢Co-translational for ER and postranlational for other organelles
➢N-terminal signal sequence (made first)
➢Signal sequence recognized by (soluble) signal recognition particle (SRP)
➢SRP binds to SRP receptor on ER membrane
➢Polyribosomes attracted to ER (RER)
➢Complex (including the ribosome) brought to translocator
➢SRP-SRP receptor release
➢Translocator transfers growing polypeptide chain through the membrane
Are Soluble Proteins fully transported across the membrane?
➢Soluble proteins are fully transported across the membrane
➢Signal peptidase cleaves off signal sequence
Transmembrane Protein
➢Transmembrane proteins are partially transported across the mebrane
➢ sequence
•start transfer
•stop transfer (hydrophobic amino acids form transmembrane domain (alpha-helix))
