Proteins - Lecture Six Flashcards
Folding a Protein
Super-secondary structure
Helix-Turn-Helix
Beta hairpin - common, anti-parallel and length varies
Greek key - Four anti-parallel strands
Strand-Helix-Strand
Protein domain
The conserved part of a given protein sequence and tertiary structure that can evolve, function, and exist independently of the rest of the protein chain
Protein families
Alpha domain, alpha-beta, and antiparallel beta
Alpha domain family
Mostly helices
Alpha-beta family
The sequence determines the pathway
Where are proteins made?
At the ribosome and then they fold into their active shape spontaneously
Where are ‘instructions’ for the protein?
Embedded in the amino acid sequence
Stabilising of protein folding
Non-covalent interactions, while individually weak, collectively make a significant contribution to protein conformational stability
Covalent bonds e.g. disulphide bonds may be present that contribute to confirmation stability
Hydrophobic core, most important non-covalent contributor in aqueous solutions
Folding pathways
Protein folding is directed largely by its internal hydrophobic residues, which form an internal core, while hydrophilic residues are solvent exposed. This is not a random process
Folding pathway steps
Formation of short secondary structure segments
Nuclei come together, growing cooperatively to form a domain
Domains come together (but tertiary structure still partly disordered)
Small conformational adjustments to give compact native structure
Chaperones
Some protein folding is assisted with chaperones
Chaperone examples
Chaperone-dependent e.g. Hsp70
Chaperonin-dependent e.g. GroEL-GroES
Unfolding of proteins
Weakening of non-covalent interactions can lead to unfolding and loss of biological function (denaturation) which can result from a change in pH, heating, detergents, organic solvents, urea (can be reversible) and granidium HCL (can be reversible)
Mis-folding of proteins in disease
Proteins in living organisms that are folded normally can sometimes change their shape and become mis-folded. Some mis-folded proteins can cause other proteins to change their shape as well, sometimes with disastrous consequences
Alpha to beta tranformation
No treatment. always fatal
Conditions in the brain due to prion related protein (PrP) that changes its shape and then forms aggregates that cause brain damage
BSE - Bocine Spongiform Encephalopathy
CSD - Creutzfeld-Jacob Disease
Kuru
