Lecture 2 revision Flashcards
What is a protein domain?
A polypeptide chain or part of a polypeptide chain that can fold independently to form a tertiary structure
What are protein domains formed from?
- Different combinations of secondary structural elements and structural motifs
- Domains recognisable units of tertiary structure
- If a domain was expressed independently of the rest of a protein, it was fold to form a stable folded structure
Can a domain be a whole protein?
Yes
triosephosphate isomerase is an example
Many B-a-B motifs link and join together to form a domain which then folds to to form a protein
Can a domain be part of a whole protein?
Yes
Pyruvate kinase is an example
Three discrete domains form the enzyme, where the same domains can appear in different proteins that perform different functions
Protein domain groupings
Levitt and Chothia determined groups based on domain structures:
a-Domains - Contain only a-helical motifs
B-domains - Contain only B-pleated sheets
a/B domains - Made up of predominantly B-a-B motifs
The coiled coil domain
- a-domain
- More general case of leucine zipper motif
- Amphipathic a-helices formed from multiple heptad repeats:
H-P-P-H-P-P-P - Hydrophobic stripe on helix
- Two stripes align to minimise solvent exposure
- Coiled coil structure reduces turns from 3.6 to 3.5 Armstrong, where hydrophobic stripes align.
Three helix bundle
- a-domain
- Three intertwined coiled-coil a-helices
- Hydrophobic residues between helices necessary
- Helices can run parallel (fibrinogen) or anti-parallel (HSc20, heat shock cognate protein).
Four helix bundle
- a-domain
- Helices more cross-over each other rather than twist around each other.
- Hydrophobic core - hydrophobic residues buried between helices
Examples include myohemerythrin (antiparallel) and human growth hormone (parallel)
The Globin fold
- Found in large groups of related proteins e.g. myo and haemoglobin
- Helix-loop-helix motifs
- Eight helices wrapped around central core - active site e.g. heme
- Helix pairs not adjacent with exception of G and H - form an anti-parallel pair
The up and down barrel
- Rolled up sheet of beta-sheet fold motifs
- Last and first strand interact via H-bonds to ‘seal’ the roll
- Can be twisted and distorted e.g. in retinol binding protein
The beta barrel
- Variation on up and down barrel bit not a simple ‘roll-up’
- Strands 4-6 flipped around so order in barrel is 1, 2, 3, 6, 5, 4, 7, 8 i.e. strands not in the same order in the 3D structure as in the continuous polypeptide chain.
Superoxide dismutase is an example
Greek key proteins
Two beta-fold motifs are folded into a Greek key motif.
Proteins made up of a succession of Greek key type folds
- Gamma-crystallin - found in lenses of eyes - responsible for maintaining smooth gradient of refractive index of light
The jelly roll
- Made up of Greek key motifs but arranged in a different way e.g. spherical virus coat proteins, concanavalin A.
- 4 continous beta strands running anti-parallel to a second four
The parallel beta-helix
- Cylinder/helix of parallel beta sheets which also contains calcium ions.
- Simplest form contains two sheets e.g. Serratia metalloproteinase - first isolated from Serratia bacterium.
- Can also contain three beta-sheets e.g. pectate lyase
The a/B barrel
- Barrel of B-a-B fold motifs - core of hydrophobic twisted B-strands surrounded by hydrophilic a-helices.
- Centre of barrel full of hydrophobic side chains.
- Active site at one end of barrel formed by loops which connect carboxyl ends of B-strands to amino end of a-helices.
Twisted sheet
- a-helices on both side of the plane of the beta-sheet; cannot form a barrel structure
- Twisted beta-sheet is found at the core of the domain surrounded on all sides by a-helices.
Horseshoe fold
Motifs that form the domain form a beta-loop-a-structure stabilised by leucine residues in the hydrophobic core which pack against each other.
Dynamic phosphorylation
Common protein modification in eukaryotes
Dynamic phosphorylation is a key mechanism of cell signalling
Occurs one serine (90%), threonine (10%) and tyrosine (<1%)
10-30% proteome is phosphorylated
effects structure, activity and localisation
Protein-OH -> Protein-PO43- by protein kinase
Protein-PO43- -> Protein-OH by protein phosphatase
N-glycosylation
- Glycosylation of asparagine (N) residues occurs co-translationally in ER
- sequence motif NX(S/T) where X is not proline
N-glycans have complex, branched structures that undergo further post-translational modification to increase diversity.
Increases hydrophilicity and modulates proteins via protein interactions
