Lecture 5: Structure of Proteins Flashcards
A functional protein is in its
native state
Do any of the 4 intermolecular forces predominate in protein folding?
No, every protein is different
What does resonance cause in the primary chain
to be quite rigid and nearly planar
What is the phi angle?
What is the psi angle?
angle around the a carbon - amide nitrogen bond
angle around the a carbon - carbonyl carbon bond
Why are some psi and phi angle unfavorable?
Because of steric crowding of backbone atoms with other atoms in the backbone or side chains
When are some psi and phi angles more favorable?
Because of chance to form favorable H-bonding interactions along the backbone
What are the blacked out areas
What are the two common secondary structures?
a helix and b sheet
What is a random coil
Irregular arrangement of polypeptide chain (not misfolded)
What are some characteristics of an alpha helix
- Helical backbone is held together by hydrogen bonds between the backbone amides of an n and carboxyl group of an n+4 amino acids
- All are right-handed helix with 3.6 residues (5.4 A) per turn
- Side chains point out and are roughly perpendicular with the helical axis
What is the inner diameter of an alpha helix and outer diameter?
Inner: 4 - 5 A
Outer: 10-12 A
What type of sequences affect helix stability
- Small hydrophobic residues such as Ala and Leu are strong helix formers
- Pro acts as a helix breaker because the rotation around the N-C angle is impossible
- Gly acts as a helix breaker because the tiny R group supports other confirmations
- Attractive or repulsive interactions between side chains 3 to 4 amino acids apart will affect formation
- Two aromatic amino acids residues are often space 3 to 4 amino acid for hydrophobic interactions
The alpha helix has a large macroscopic dipole moment. Where do negative charged residues often occur?
Near the positive end of the helix dipole. This is a favorable interaction and help stabilize
Why do beta sheets occur and some characteristics?
- Due to planarity of the peptide bond and tetrahedral geometry of the alpha carbon
- Sheets are held together by the hydrogen bonding of amide and carbonyl groups of the peptide bond from opposite strands
- Side chains protrude from the sheet, alternating in an up-and-down direction
What are the two directions of the B sheets
Parallel: strands that are oriented in the same direction
Antiparallel: strands that are oriented in the opposite directions
Is the hydrogen bonding within parallel sheets strong or weak?
Weak due to bent orientation
Is the hydrogen bonding in antiparallel b sheets strong or weak?
Strong
What are B-turns
- Occur frequently whenever strands in B sheets change direction
- The 180 degree turn in accomplished over four amino acids
- The turn is stabilized by a hydrogen bond from a carbonyl oxygen to amide proton three residues down the sequence
- Proline in position 2 (type I) or glycine (type II) in position 3 are common in B turns
- normally near surface where hydrogen bonds can occur with position 2 and 3.
What configuration are most peptide bonds in?
Without profile they are 99.95 in trans configuration
With proline, about 6% are in the cis configuration and they are in B turns
What are tertiary structures?
the overall spatial arrangement of atoms in a protein
How are tertiary structure stabilized?
Stabilized by numerous weak interactions between amino acid side chain
What are the two major classes of tertiary structure?
Fibrous and globular (water and lipid soluble)
What are motifs?
What are some common ones (2)
Specific arrangement of several secondary structure elements
What is a quaternary structure?
Is formed by the assembly of individual polypeptides into large functional cluster
What type of protein structure is keratin
a-helix, cross linked by disulfide bonds
What type of protein structure is collagen?
3 intertwined chain create right handed triple helix
Each collagen chain is a long Glycine and Proline rich left handed helix
higher tensile strength than steal
How are collagen superstructures formed?
Formed by cross-linking of collagen triple-helices to form collagen fibrils
Cross links are covalent bonds between Lys, His, or HyLys residues
What is Fibroin
Antiparallel B sheet structure
small side chain (Ala and Gly) allow the close packing
Stabilized by hydrogen bonding and london dispersion
What four ways can protein be denatured
Heat/Cold
pH extremes
Organic solvents
Chaotropic agents (urea)
How is protein folding done so fast?
Search for lowest energy conformation is not random because the direction toward the native structure is thermodynamically most favorable
What causes Alzheimer’s disease
- B amyloid is soluble globular protein
- Misfolded B amyloid promotes aggregation at newly exposed protein-protein interface
- Peptide forms B strands, B helices, and B sheets
- insoluble plaques aggregate and deposit in cells
