Chapter 4 Flashcards
(25 cards)
What are the weak interactions that contribute to the native conformation of proteins?
hydrophobic effect, hydrogen bonds, london disperison, electrostatic interactions
What are the properties of peptide bonds?
there is no freedom of rotation because it has a double bond character due to resonance
Where are f(phi) bonds?
angle around the amide nitrogen and alpha carbon bond
Where are the y(psi) bonds?
angle around the alpha carbon and carbonyl carbon bond
What are the properties of the phi and psi bonds?
~they can rotate +/- 180 degrees in the most extended conformation
they form an alpha helix
~some combinations are unfavorable because of steric hinderance
~some are more favorable bc they can form favorable H-bonding interactions along the backbone
Describe the features of the alpha helix
~backbone is held together by hydrogen bonds between the backbone amides
~peptide bonds are aligned roughly parallel with the helical axis
~side chains point out and are roughly perpendicular with the helical axis
~the outer diameter fits well into the major groove of dsDNA
What affects helix stability/formation?
~small hydrophobic residues like Ala and Leu are strong helix formers
~Pro and Gly are helix breakers
~attractive or repulsive interactions between side chains 3-4 amino acids apart will affect formation
~placement of “like” amino acids on one side of the helix can produce an amphipathic helix
Describe the helix dipole
~peptide bond has a weak dipole moment ( carbonyl O neg; amide H pos)
~the alpha helix has a large macroscopic dipole moment
~negatively charged residues often occur near the N-terminal end of the helix dipole and positively charged amino acids are found at the C-terminal end
Describe beta conformation
~highly extended into a zigzag structure (chain); beta strands can be arranged side by side into beta sheets
~the planarity of the peptide bond and tetrahedral geometry of the alpha carbon create a pleated sheet-like structure
~the sheet arrangement is held together by hydrogen bonds
~R-group side chains protrude from the sheet alternating in up and down direction
How are parallel beta sheets arranged?
~the H-bonded strands run in the same direction which results in bent H-bonds (weaker)
How are antiparallel beta sheets arranged?
the H-bonded strands run in opposite directions resulting in linear H-bonds (stronger)
Describe the features of beta turns
~occur frequently whenever strands in beta sheets change the direction
~180 degree turn is accomplished over 4 amino acids
~the turn is stabilized by a hydrogen bond from a carbonyl oxygen to amide proton three residues down the sequence
~proline (causes kinks) in position 2 or glycine (small and mobile) in position 3 are common in beta turns
What is the tertiary structure of a protein?
refers to the overall spatial arrangement of atoms in a protein
How are tertiary structures stabilized?
~by weak interactions between amino acid side chains:
~largely hydrophobic and polar interactions
~can be stabilized by disulfide bonds
What are the two major classes of tertiary structure
fibrous and globular (water or lipid soluble)
describe the structures and properties of fibrous proteins
~alpha helix cross linked by disulfide bonds: tough, insoluble protective structures of varying hardness and flexibility (keratin of hair, feathers, nails)
~ beta conformation: soft, flexible filaments (silk fibroin)
~collagen triple helix: high tensile strength, without stretch (collagen of tendons, bone matrix)
Describe the structure of hair
1) keratin alpha helix
2) 2-chained coiled coil
3) protofilament
4) protofibril
~insoluble in water
~contains disulfide bonds
~flexible without breaking
Describe the biosynthesis of collagen
- hydroxylation of Pro and Lys residues; assembly of triple helix in endoplasmic reticulum
- packing in golgi and secretion
- cleavage of N and C terminal non-helical segments
- cross-linking at lysine and hydroxylysine residues and assembly into fibrils
- aggregation of fibrils into collagen fibers
Describe the structure of collagen
~each collagen chain is a long Gly and Pro rich left-handed helix
~3 collagen chains intertwine into a right-handed superhelical triple helix
~common configuration: Gly-X-Y where gly is typically every 3rd residue, X is often proline, and Y is often hydroxyproline or hydroxylysine
describe symptoms Osteogenesis imperfecta type 1
Mutation in collagen gene COL1A1 Characterized by: Fractures common before puberty Near normal stature Spinal curvature common blue sclera hearing loss Least severe type
describe symptoms of Osteogenesis imperfecta type 2
Mutation in COL1A1 or COL1A2
Characterized by: Most severe type (lethal) Bone deformity and small stature Underdeveloped lungs etc.
what is the biochemical mechanism of Osteogenesis imperfecta type 1
reduced COL1A1 mRNA (haploinsufficiency- 50% of the protein is not enough for normal bone structure).
what is the biochemical mechanism of Osteogenesis imperfecta type 2
amino acid substitution in COL1A1 or COL1A2 genes from glycine to another amino acid. Substitutions that are not conserved (glycine to amino acid with a large or charged R group) compromise the triple helix formation so that bones cannot form or mineralize properly
Describe ehlers-danlos syndrome
The “Classical” type of EDS results from mutations in either the COL5A1, COL5A2, and the COL1A1 genes
Some forms of EDS are caused by improper processing of collagen (at 1 and 3 step in making collagen) related to mutations in the ADAMTS2 gene and PLOD1 gene
