Describe characteristics of an α-helix.
usually right-handed
stabilized by h-bonds between NH---O=C (with 4 aa distance)
polarity (- at C- end, + at N-terminus)
can be used to coordinate, ions, etc. phosphate
all-α proteins usually have four-helix bundles (very stable due to hydrophobic side-chain interactions) or the globin fold (eight helices)
by the composition and distribution of polar and unpolar residues, you can deduce the position of a helix in the protein (inside: hydrophobic, outside: hydrophilic)
Describe the characteristics of a β-strand/sheet.
sheets are made of strands
parallel and antiparallel sheets possible
stabilized by H-bonds between NH---H=C between different strands
sheet formation requires loops/turns between strands, normally 3-6 aa long
typical folds:
β-barrel
β-propellor (e.g. in signal transduction)
β-helix
Which interaction play a role in the formation of secondary structures?
most stable structure elements form first
involved forces
hydrophobic effect (hydrophobic parts assemble fast because they cannot interact with the surrounding water)
H-bonds
salt bridges
electrostatic interactions
disulfide bonds
What characterizes all-α, all-β, α/β, α+β and cross-linked proteins?
- all- α
o four-helix bundles (very stable due to hydrophobic side-chain interactions)
o globin fold (eight helices)
- all-β
o β-barrel
o β-propellor (e.g. in signal transduction)
o β-helix
- α/β
o β-α-β motif
o (βα)8 barrel / TIM barrel (triosephosphatisomerase): “Bottom” is closed with big hydrophobic residues, “top” is open
- α+β
o α- and β-structures/clusters are separated from one another
- cross-linked
o disulfide linkages between secondary structures
o coordination of ions as a linkage (e.g. zink finger)
What is a protein domain?
A protein domain is a part of a protein that folds independently of the rest.
- typical size: 200 aa
- usually hydrophobic core
- multidomain enzymes: different domains have different functions
- sometimes, two domains of a protein do not follow after one another in the aa sequence, but one domain “interrupts” the other
What are Structural Genomics/Proteomics?
- goal: find out structure of every protein encoded in a certain genome
- combination of experimental and modeling approaches
- methods:
o high-throughput cloning of open reading frames
o express encoded proteins
o purification, crystallization
o modeling based on sequence
What is the “dark” part of the proteome?
intrinsically disordered protein (parts)
What processes are intrinsically disordered proteins involved in?
- transcription
- transcription regulation
- cell cycle
- mRNA splicing
- apoptosis
- protein transport
Why is it useful that parts of a protein are disordered?
- adaptability to different binding partners
- high specificity, but low affinity (fast association/dissociation)
- advantage or disadvantage: unfolded proteins often aggregate because their hydrophobic parts might be exposed
Explain two binding models for disordered regions/proteins.
- folding upon binding: The region is disordered and only folds when the substrate is met
- conformational selection: The final conformation of the disordered protein is present some of the time, and when the substrate binds is “fixed”
- combination of both models possible
How do you find out if a protein is disordered?
- size exclusion chromatography:
o unfolded proteins travel slower than folded proteins of the same size because they have a higher radius
- circular dichroism
o random coils do not show typical patterns of secondary structure
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