Exam 2: Chp 6 Flashcards
What is protein folding?
The process of adopting secondary, tertiary, and quaternary structure
What is a native protein?
A folded protein with correct structure and that can perform function
What is a denatured protein?
An unfolded protein, typically has lost function`
What non covalent forces facilitate protein folding?
H-bonds, hydrophobic interactions, ionic interactions, and Van der Waals,
How do we know that all information for folding is contained in primary structure?
Because we can observe side chains interacting to produce specific structure that produces specific function
What is the angle of rotation around the N-C⍺ called?
Phi ɸ
What is the angle rotation around the C⍺-Co bond called?
Psi ψ
Does a negative angle of rotation in a polypeptide indicate clockwise or counterclockwise?
Counterclockwise
What phi and psi values are not allowed and why?
ɸ = 0 and ψ = 180, or ɸ = 180 and ψ = 0 due to steric strain
What is a ramachandran plot?
A plot of phi and psi angles for a protein or family of proteins
What stabilizes ⍺-helices?
H-bonds in the backbone
How many residues per turn in an ⍺-helix?
3.6 residues per turn
What are the phi and psi angles of a right-handed alpha-helix?
phi = -60, psi = -50
What are phi and psi angles of a left-handed alpha-helix
phi = +60, psi = +60
How does H-bonding in an alpha helix organize?
Every 4th AA H-bonds to the next to create the helix backbone
Is the ⍺-helix charged? in what way?
A net dipole with a negative C-term and positive N-term
What amino acids destabilize a helix? Why?
Glycine minimizes sterics that keep it in ⍺-helix position and proline ring resists psi and phi angles necessary for helix
What are β-sheets made out of?
β-strands
How many residues does a β-strand have per turn?
2
What direction to adjacent residues on a β-strand face?
one faces up and the other down
How do β-strands interact to form a β-sheet?
via backbone h-bonds
What are the two arrangements of β-strands in a β-sheet?
parallel or antiparallel
Describe antiparallel arrangement of β-strands
The N and C-terminals are on opposite sides
Describe parallel arrangement of β-strands
The N and C-terminals are on the same side
What are the phi and psi angles of parallel β-strands?
phi = -120, psi = 105
What are the phi and psi angles of antiparallel β-strands?
phi = -135, psi = 140
What is a β-turn?
A hair-pin turn in a polypeptide chain resulting from an H-bond of a carbonyl oxygen and an NH that is 3 positions away
What structure connects antiparallel β-sheet?
β-turn
What structure connects parallel β-strands?
an ⍺-helical component
What kind of proteins are ⍺-keratins?
fibrous
What is the monomer of ⍺-keratin?
a central right handed ⍺-helix called with rod domain with globular N and C-terminals
What is the dimer of ⍺-keratin?
2 monomers form a left-handed coiled-coil
What is a coiled-coil?
two ⍺-helices twisted around each other
What is a protofilament?
A pair of ⍺-keratin dimers stacked next to each other with bonding interactions
What is a protofibril?
A pair of ⍺-keratin protofilaments
What makes up a final ⍺-keratin filament?
4 protofibrils twisted together like a rope
Why do coiled coils form?
Each monomer has heptad repeats where residues 1 and 4 are non polar; 1 and 4 line up for create a non-polar strip which congregates with strips of other monomers (stabilizing H-bonds)
Why do protofilaments and protofibrils form?
H-bonding is stabilizing and keratin is rich in Cys creating S-S bonds
What causes nails to be more rigid or hair to be curlier?
More covalent interactions between protofilaments or protofibrils
What type of protein is collagen?
fibrous
What is the monomer of collagen?
a left handed helix that is around 1000 AAs long
How many residues does a collagen monomer have per turn?
3.3 residues per turn
Why are collagen monomers unique?
They are a LEFT-handed ⍺-helix and are tighter because they are high in glycine and proline
What are common modifications to collagen AAs?
Prolyl hydroxylase modifies proline to hydroxyproline (Hyp) and Lysol hydroxylase modified lysine to hydroxylysine
Why is collagen commonly modified by propol hydroxylase and lysol hydroxylase?
Because hydroxyproline and hyroxylysine provide more opportunities for H-bonds, tightening the ⍺-helix
What is tropocollagen?
A right-handed triple helix formed by 3 collagen monomers
What is the common AA sequence of collagen monomers?
Gly-X-Y motif (repeat)
Where is Glycine located in tropocollagen helix and why?
the center because it is the only AA small enough
Where are proline and hydroxyproline located in a tropocollagen helix?
The outside
What stabilizes a tropocollagen helix?
H-bonds with side chains and backbone atoms
What is a collagen fiber made of?
Associated tropocollagen fibers
What stabilizes collagen fibers?
covalent cross links between tropocollagens
What is a Schiff base?
When a lysine of a tropocollagen is oxidized to allysine then reacted with another lysine to form an imine linkage
What are 2 ways tropocollagen fibers can be linked together?
1) Schiff base
2) aldol condensation between allysines
What is the goal of tertiary structure?
To form the most stable structure possible by maximizing non-covalent interactions
What are 4 themes are globular tertiary proteins?
1) ⍺-helices and β-sheets in core
What are domains?
distinct regions globular regions of proteins that make up the 3° structure and form together to complete a protein
What about protein folding suggests that it is cooperative?
Once folding or denaturing begins, it completes very quickly
What are the 3 steps of protein folding?
1) 2° structure forms first
2) hydrophobic collapse where non polar AAs aggregate in center
3) Long range interactions between 2° structures and final hydrophobic interactions
What is the funnel model of protein folding?
Proteins goes through stages of folding where it reaches lower energy conformations and must reverse in energy and conformation to return to the original folding path
What is the largest contributor to change in free energy during protein folding>
entropy of water
Why are proteins dynamic and folding reversible?
change in free energy is not too large
What is x-ray crystallography? A downfall?
the most common way to determine protein structure; does not capture dynamic state?
What are molecular chaperons?
proteins that help other proteins fold into correct shape; prevent misfolding
What are intrinsically unstructured proteins (IEPs)?
Proteins without a defined folded tertiary structure
Why are IEPS mobile?
Because they are rich in proline and polar residues, preventing hydrophobic collapse
What is an advantage of IEPs?
They can bind to many ligand and perform many different reactions
What are two disadvantages of protein misfolding?
loss of function and protein aggregation
Why do misfolded proteins aggregate?
Nonpolar AAs that would typically be in the center of the protein are exposed
What are homomultimers?
Quaternary protein with multiple of the same polypeptide chain
What are heteromultimers?
Quaternary protein with multiple of different polypeptide chains
Is transition from 3° to 4° structure favorable or unfavorable? Why?
unfavorable because entropy is lost
Why do 4° structures form even though entropy is lost?
the gain is stability outweighs the loss in entropy
What are 4 advantages to 4° structure?
1) stability
2) less genetic input for more product
3) Brings catalytic sites together
4) Cooperativity of subunits
What is common amino acid of a β-turn?
Proline
