Chapter 4: The Three-Dimensional Structure of Protein Flashcards
What gives the C-N bond in a peptide bond partial double bond character?
Resonance
What hybridization does C and N have in a peptide bond?
sp^2 hybridization (trigonal planar)
What determines the conformation of the polypeptide backbone (main chain)?
The rotation of the planar peptide groups around single bonds (N-Cα bond and Cα-C bond); the single bonds are rotated about the α-carbon.
What describes the conformation of the peptide backbone?
Dihedral (torsional) angles; each residue has a pair of dihedral angles.
- Φ (phi) = N-Cα bond
- Ψ (psi) = Cα bond
Are most peptide bonds cis or trans?
Trans (ω = ± 180°)
- ω is the dihedral angle for the peptide bond.
- cis-peptide bonds (ω = 0°) are sterically unfavorable (side chain steric clash)
What are the two most common secondary structural protein elements?
- α-helices
- β-strands (which assemble into β-sheets)
What is a helix?
A helix is a curve formed from repeating units in which evert point on the curve has the same distance and angle from a central axis.
What end is positive and what end is negative in an α-helix?
N-terminal end is positive.
C-terminal end is negative.
- This is because an α-helix has a net dipole moment.
What are two examples of amino acids that cannot form a helix?
- Proline - too rigid, can’t donate H bonds.
- Glycine - too much flexibility.
Where are negatively charged side chains usually found in an α-helix? What about positively charged side chains?
Negatively charged side chains are often found in the first turn of a helix (N-terminal end).
Positively charged side chains are often found in the last turn (C-terminal end).
Where are amphipathic α-helices found on a protein?
Amphipathic α-helices are found on the outside of a folded protein.
- Hydrophobic side chains are on one side of α-helix.
- Polar/uncharged on the other (to interact with solvent).
What direction are C=O and N-H bonds pointing in β-strands? What about R groups?
C=O and N-H bonds are pointing side to side.
R groups alternate up and down to avoid sterics.
What are the two primary types of reverse turns in backbone conformations?
γ-turns (only one residue involved in the turn)
- Residues 1 and 3 (i and i+2) H-bond with each other.
β-turns (two residues involved in the turn)
- Residues 1 and 4 (i and i+3) H-bond with each other.
What are the two types of β-turns?
Type I: residue 2 is Proline (sometimes cis).
Type II: residue 3 is Glycine.
What does a Ramachandran plot show?
Shows Φ, Ψ values for the residues in a protein.
- Most parts of the plot are “forbidden” due to steric repulsion.
- A large number of residues have similar Φ, Ψ values that correspond to regular secondary structural elements.
What is the 3,10 helix?
- More tightly wound than α-helix.
- Less common
- Right-handed helix
- Usually found as extension at the end of α-helix (first or last turn or two)
What do most proteins fold up into?
Globular shape
What are fibrous proteins?
- Rod-like or sheet-like molecules within a single uniform secondary structure
- Generally insoluble
What roles do fibrous proteins take?
Structural or mechanical roles
What are globular proteins?
- Super compact protein that consists of one or more structural domains
- Can be primarily α, primarily β, or contain both
- Highly diverse in structure and function
- Most are soluble in water
What are motifs?
A combination of adjacent secondary structural elements
What are the four different types of motifs?
- β-α-β motif
- β-β-β motif
- α-α motif
- Greek key motif
What are formed my motifs?
Domains (compactly folded unit of protein)
What are the three classifications of domain structures?
- α domains: folds containing only α-helices
- β domains: folds containing only β-sheets
- α/β domains: folds containing both α-helices and β-sheets
What is a quaternary structure?
The assembly of multiple polypeptide chains into a functional protein through primarily non covalent interactions.
What are protomers?
Identical polypeptide chains which assemble into homodimers, homotrimers, homotetramers, etc.
What are three important examples of fibrous proteins?
α-keratin
fibroin
collagen
What is keratin?
A fibrous protein found in all higher vertebrates.
- Homodimer of two α-helical keratin polypeptide chains wrapped around one another to form left-handed superhelix (coiled coil)
- 7 amino acid repeating unit (abcdefg) where a and d are hydrophobic (often Leu)
- Skin, hair, wool, fingernails, hooves, horns
What is collagen?
A triple helical cable of collagen helices.
- Most abundant protein in vertebrates.
- Skin, bone, tendon, blood vessels, cornea
- Left-handed helix, 3 residues per turn
- Formed from repeating units of Gly-X-Y (X is usually Pro, Y is usually 4-Hyp)
What is the most thermodynamically stable state of a protein?
Native or folded state.
What does it mean when a protein is denatured?
When protein structure is disrupted to the point that biological activity is lost.
What is cellular proteome?
An entire set of proteins produced at a given time in a given cell under given conditions.
What is proteostasis?
The dynamic regulation of a functional cellular proteome.
What happens when a protein is no longer needed?
It can be tagged for destruction with ubiquitin and transferred to the proteasome, where it is broken down.
- Misfolded proteins are also tagged for degradation.
What are molecular chaperons?
Proteins that assist in protein folding, rescue unfolded proteins, and disrupt nonfunctional protein aggregates.
What are amyloidoses?
Misfolded/partially folded secreted proteins that associate via β-sheets to form long amyloid fibril
- Insoluble fibrils accumulate in affected tissues and cause damage/cell death
