Week 4 Flashcards
Which amino acid does transcription always start with?
Methionine
Which of the following post-translational modifications targets the protein for destruction?
Ubiquitination
What proteins are degraded in the lysosome?
- Long half-life
- Membrane proteins
- Extracellular proteins
What proteins are degraded in the proteasome?
- Short half-life
- Key metabolic enzymes
- Defective proteins
What are the different levels of protein folding?
- Primary: amino acid sequence
- Secondary: local folding
- Tertiary: long-range folding
- Quaternary: multimeric organisation
- Supramolecular: large scale assemblies
What is proteostasis?
Protein homeostasis
involves; synthesis, folding, processing, assembly, trafficking, localisation and degradation
What causes secondary bonding in the alpha helix?
- H bonds forming between each carbonyl oxygen atom of each peptide bond with the amide H atom from an amino acid
- Results in a periodic spiral
- Confers directionality on the helix
- R groups face outwards, covering the helix
What causes secondary bonding in the beta sheet?
- Each strand is 5-8 amino acid residues
- Hydrogen bonding between strands of polypeptide forms the planar sheet
- Directionality: parallel, anti-parallel
- R groups project from both faces of the sheet
What factors affect protein folding?
- proteins self-assemble into a 3D conformation
- Protein conformation is determined by its primary structure
- hydrophobicity is an important determinant of final conformation
BUT - considerable variation in time taken for a protein to adopt a final conformation
- cellular environment is highly crowded
- increased tendency for proteins to aggregate
What are molecular chaperones?
- Any protein that interacts with, stabilises or helps another protein to acquire its functionally active conformation, without being present in its final structure
- Selectively bind to short stretches of hydrophobic amino acids
- Different classes of structurally unrelated chaperones exist, forming cooperative pathways and networks
- Proteome-maintenance functions:
- de novo folding
- refolding
- oligomeric assembly
- protein trafficking
- proteolytic degradation
What stabilises tertiary structure of proteins?
Interactions between R groups:
- hydrophobic interactions between non-polar R groups
- hydrogen bonds between polar R groups
- disulphide bonds
How do molecular chaperones encourage folding?
- Nascent polypeptide leaves ribosome
- As polypeptide leaves ribosome chaperons begin to bind
- More chaperones bind until protein emerges from ribosome
- Chaperone forms cover for protein to fold into its final conformation
What percentage of newly synthesised proteins are misfolded?
30%
How are mis-folded proteins re-folded in the ER?
- Newly synthesised glycoprotein has all but one sugar groups removed by glucosidease I & II, creating a binding site for chaperones
- Chaperones create environment for proteins to correctly fold
- After folding occurs glucosidase II removes last sugar group and if protein is correctly folded it leaves the ER
- If protein is not correctly folded glucosyltransferase detects hydrophobicity and reattaches sugar group for further folding, or degrades protein in ribosome
Describe the proteasome:
- Protein-degrading machines
misfolded
short-lived
- Cytosol and nucleus
- Hollow, cylindrical structures
CAP
alpha-subunits (non enzymatic)
beta-subunits (proteolytic activity)
