Lecture 5: Three-dimensional Structure Of Proteins Flashcards
What is the protein structural hierarchy?
•Quaternary structure (Assembled subunits)
•Tertiary Structure (Polypeptide chain)
•Secondary structure (Alpha Helix)
•Primary Structure (Amino Acid)
What does stability mean in protein structure?
•Tendency to maintain a confirmation; its native conformation
The unfolded state of a protein can have countless conformations
•Entropically driven
•H-bonding with water
The chemical interactions that drive protein structure are largely
Non-covalent interactions with the exception of disulfide bonds in proteins
Protein conformation or structure, overall, is driven by
Having the lowest free energy state (G)
Having the lowest free energy state is achieved when
The maximum number of non-covalent interactions are formed in a protein
The stability of protein is NOT
The sum of its non-covalent interactions
Non-covalent interactions in proteins
•Hydrophobic effect
•Ionic interactions
•Hydrogen Bonding
•Van der Waals
Hydrophobic effect
•Increased arrangement of water around a hydrophobic molecule
•Entropically unfavorable (decreases entropy)
•Hydrophobic molecules will cluster
•Decreases the total amount of arranged water (increases entropy)
What is the Hydrophobic effect in proteins?
•Clustering of the nonpolar (hydrophobic) amino acid side chains within the interior of a protein
•Shielded from the aqueous environment
•Creates a hydrophobic core
Polar interactions
•Hydrogen bonding
•Ionic interactions/ Electrostatic interactions
•Involve non-covalent interactions between amino acids or with aqueous (water) solvent
•Includes polar and charged amino acids
Polar groups in proteins can have hydrogen bonding partners by…
-With peptide backbone or other side chains (R groups)
-With the aqueous environment
Presence of polar groups in the hydrophobic core is
Destabilizing
Hydrogen bonding within a protein occurs cooperatively because
Formation of one h-bond makes the formation of another more likely
Polar interactions for charged amino acids
•Can be stabilizing or destabilizing
•Charged amino acid chains can interact with water and other ions of the aqueous environment
•H-bonding
•Salt bridge interactions-ionic interaction
Van der waals interactions
•Distance Dependency
•Dipole-Dipole interactions
•Can occur between hydrophobic amino acids side chains
Alpha helix
•3.6 residues per turn of the helix
•5.4 A between repeating units in turns
•R groups protrude outward
•Defined by a set of dihedral angles
How is the A-helix structure stabilized?
•Hydrogen bonds (Intrahelical H-bonds)
•Between the hydrogen of the amine group (residue 1) and a carboxyl-oxygen (residue 4)
•Extensive hydrogen bonding network gives significant stability of this secondary structure
A-helix can have “faces”
• Arrangement of R-groups can give chemical characteristics to the helix
•Gold balls means residues are hydrophobic amino acids
•Colored balls mean charges residues
•Helices in proteins are right handed
R-group considerations and the adjoining amino acids (A-helix)
•Potential non-covalent interactions
•Potential steric clash
A-helices
•Helices have a dipole
•Common to fine negative amino acids toward the N-terminal
•Common to find positive amino acids towards the C-terminal
B conformation; B-sheet
•Extended “zig-zag” conformation
•R-groups protrude in an alternating directions from the plane of the peptide backbone
B-sheet
•Different dihedral angles from a helix conformation
•pleated sheet arrangement
•Can be antiparallel or parallel (defined by the orientation of the termini in arrangement)
•H-bonding occurs between sheets in this structure
B-turns
•Tight turn structures in proteins (only 4 amino acids in motif)
•Usually proline/and or glycine present
•Several types described and defined by a set of phi and psi angles
•R groups in the turn do not typically interact with each other within the turn
Helical propensities
•Poly-alanine readily forms a helix in solution
•Proline is a “helix-breaker” (rare in helices)
•Proline is a rigid amino acid and has no hydrogen on the amine group to participate in hydrogen bonding
•Glycine has a lot of conformational flexibility, its r group is hydrogen
