2.5 - Protein Folding and Function Flashcards
motif
collection of secondary structure elements (e.g. binding motif)
domain
distinct functional/structural unit, usually responsible for a particular function or interaction contributing to the overall function of protein
tertiary structure
3D structure of single polypeptide chain
quaternary structure
association of more than one polypeptide chain
protein folding step by step (3)
- extended chain
- disordered globule
- native highly ordered conformation
structure of disordered globule (step 2 of protein folding) (2)
- hydrophobic inside
- hydrophilic outside
structural factors which influence thermodynamics and kinetics of protein folding (3)
- size
- amino acid content
- hydrophobic/hydrophilic content
bonding factors which influence thermodynamics and kinetics of protein folding (2)
- strength of intramolecular interactions
- number of S-S bonds
domain factors which influence thermodynamics and kinetics of protein folding
domain architecture
how can some proteins fold themselves?
driven by hydrophobic burial and/or formation of secondary structure elements
chaperones
also called heat shock proteins (Hsp)
role of chaperones (3)
- few proteins can achieve active conformation unaided
- during stress, proteins unfold and need to reassemble
- protein complexes may require help from chaperone to form/be broken down
mechanism of chaperones aiding protein folding (3)
- unfolded polypeptide enters chaperonin cylinder from one end
- cap attaches to end causing cylinder to change shape creating a hydrophilic environment for polypeptide foldinh
- cap comes off and folded protein released
what happens if protein folding goes wrong? (2)
- protein doesn’t function as it should
- can aggregate and accumulate
result of amyloid plaques
BSE, CJD and Alzheimer’s disease show numerous amyloid plaques that cause spongiform degeneration
amyloid self-assembly (6)
- monomer
- aggregate
- oligomer
- protofibril
- amyloid fibril
- amyloid plaque
structural property of amyloid plaques
very stable, due to self assembly
cellular prion protein (4)
- 50% a-helix content
- 20% b-sheet content
- single disulphide bond
- flexible polypeptide tail
what causes prion disease
misfolded protein
prion diseases (2)
- infectious
- causes brain tissue to become ‘spongy’
drawbacks of electron microscopy in observing 3D protein structures (2)
- need protein large enough to see, and with regular structure
- relatively low resolution (10-50 A)
requirement for X-ray crystallography
soluble protein that will crystallise and diffract
requirement for nuclear magnetic resonance (NMR)
soluble protein that is quite small
stages of microscope (2)
- light strikes object and is diffracted in various directions
- The lens collects diffracted rays and reassembles them to form an image
benefit of X-rays in observing 3D protein structure
can detect diffraction from molecules
drawback of X-rays in observing 3D protein structure (2)
- have to use computer to reassemble diffraction image
- scattering from single molecule = very weak (signal could not be detected above noise)
benefits of using X-ray crystallography to observe 3D protein structure
arranges identical molecules in a lattice so scattered waves can add up in phase and raise the signal to a measurable level (acts as an amplifier)
what do waves adding up in certain directions and cancel out in others result in X-ray crystallography?
diffraction pattern made up of spots
