Chapter 6 Flashcards
Phi angle
between the N-terminus and alpha C (-180o,180o)
Psi angle
The angle between the alpha carbon and the carbonyl carbon (free rotation)
omega angle
the angle between the carbonyl carbon and N, this angle is rigid planar because of the delocalization of electrons through their bonds, which give them both double bond character
Ramachandran plot
- Assumption is that polypeptide chain is made up of all L-alanines
- Shows the possible phi and psi angle combinations
- Certain regions on plot correspond to different secondary structures
- Parallel, antiparallel beta sheets and polyproline II helices are found in upper right corner blob of chart
- Middle left corresponds to alpha helices, pi helices, and 310 helices
- upper right hand quadrant is left-handed alpha helices
Why is glycine special for ramachandran plots?
Glycine is the least conformationally restricted amino acid residue because its side chain is just an H. It can be found in nearly all regions on a ramachandran plot.
Why is Proline conformation special?
- Proline is the most conformationally restricted amino acid.
- Proline can form a cis or trans peptide bond
- ring structure prevents free rotation around phi bond (limited to -60+/-25o)
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Describe secondary structure
- the specific geometric shape caused by intramolecular and intermolecular hydrogen bonding of amide groups.
- Alpha, pi, polyproline II, 310 helices, parallel and anit-parallel beta sheets
Tertiary structure
- a description of the complex and irregular folding of the peptide chain in three dimensions.
- Tertiary structure is stabilized by interactions between R-groups. These interactions include:
- Hydrogen bonds between polar R groups
- Ionic bonds between charged R groups
- Hydrophobic interactions between nonpolar R groups
- Covalent bonds (disulfide bond)
Quaternary structure
- Interactions bewteen different polypeptide chains of the protein
- The forces that hold tertiary structure together are the same as quaternary structure
Interactions that stabilize primary structure
Peptide bonds = amide bonds beteen the carbonyl carbon of one amino acid and the Nitrogen of another amino acid
Stabilization of secondary structure
- alpha helices are stabilized by hydrogen bonds between backbone amino and carbonyl groups and those in the next turn of the helix
- Beta pleated sheets are stabilized laterally between backbone carbonyl oxygen and amino hydrogen atoms
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R groups usually found on interior of protein (hydrophobic)
Val, Leu, Ile, Phe, Met
Amino acids that tend to be on the outside of a protein (charged polar)
Lys, Arg, His, Asp, Glu
Amino Acids found on both the inside and outside of proteins (charged nonpolar)
Thr, Ser, Asn, Lys, Tyr, Trp
Keratin
- Helix of Helices
- Left handed coiled coil
- every third or fourth amino acid has a nonpolar amino acid residue so that two adjacent keratin fibers can link through disulfide bonds
- Protofilaments (one strand) dimerize top form protofibril
- Multiple protofibrils make up cells of hair, nails, etc.
Collagen
- Triple helical stucture
- left handed helices
- wrapped together in right handed sense
- basic unit called tropocollagen
- Rich in glycine and proline
- Hydrogen bonding between glycine H and carboxyl O of multiple strands
- Tropocollagen pack together into fibrils
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Domain classes in CATH
mostly beta, mostly alpha, both alpha and beta, or little secondary structure
barrel structure
several antiparallel beta sheets wrapped around to form a barrel
Conformational entropy of protein folding
The decrease in conformational energy upon folding must be compensated for by other factors
Electrostatic forces
- Ionic interactions known as salt bridges
- Relatively strong but do not contribute to stability of protein’s native state
- Salt bridge formation decreases entropy of folded protein
dipole-dipole forces within protein
weak forces, but significantly strengthen folded protein structure
Many interactions within interior of protein
Hydrogen bonding forces in protein
H-bonding within interior of protein stronger than on outside (high polarity)
Where are the H-bonds?
- between backbone atoms
- between polar side chains and backbone
- between polar side chains
Molten globule phase of protein folding
- Hydrophobic groups collapse, lowering entropy, expelling water molecules
- Partially folded intermediate, side chains still very disordered
- Significant formation of secondary structures
- Very short time frame (a few milliseconds)
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Intermediate folding
- Secondary structure becomes stabilized
- Tertiary structure begins to form
- 5-1000ms
final folding phase
- Native core packing
- H-bonding occurs in the core
- Remaining water molecules expelled from core
- tertiary structure becomes stable
- Time frame a few seconds
Energy landscape model
- Many possible paths to the native state of proteins, with many intermediates possible at different energy levels.
- The protein can get stuck at local energy minimas, which creates intermediates.
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Protein Disulfide Isomerase
- aids in the formation of native disulfide bonds
- To begin, there are several non-native disulfide bonds within protien
- PDI comes in and temporarily disulfide bonds with sulfur atom, and guides that section of protein to native disulfide bonds
Molecular chaperones
facilitate proper folding and reduce aggregation
GroEL-GroES
- Greatly increases rate of protein folding.
- ATP and protein enter GroES subunit
- ATP hydrolysis within ES causes conformational change within EL and allows for proteins to enter EL
