Protein Structure Flashcards
Structure of Proteins
• Unlike most organic polymers, protein molecules adopt a specific three- dimensional conformation.
• This structure
–> is able to fulfil a specific biological function
–> is called the native fold.
–> has a large number of favourable interactions within the protein
The polypeptide chain
polypeptide chain consists of a constant backbone (periódico) and variable side chains
The structure of the protein is partially dictated by the properties of the peptide bond
Primary Structure: The peptide bond
The peptide bond is a resonance hybrid of two canonical structures! (Ligeira deslocalização dos e- no plano –> caráter parcialmente duplo)
The peptide bond is essentially planar –> constrangimento estérico, não há rotação livre
–> Six atoms (Cα, C, O, N, H, and Cα) lie in a plane. Thus rotation about the bond is prohibited.
Polypeptide chain (rotation)
The Polypeptide Is Made Up of a Series of Planes Linked at α Carbons
Rotation around bonds connected to the α carbon is permitted.
(phi) : angle around the α carbon — amide nitrogen bond
(psi) : angle around the α carbon — carbonyl carbon bond
The rotation about the Φ and ψ bonds, called the torsion angle, determines the secondary structure
Distribution of phi and psi Dihedral Angles
Not all torsion angles are permitted!!
Some phi and psi combinations are more favourable because of chance to form favourable H-bonding interactions along the backbone
Some phi and psi combinations are very unfavourable because of steric crowding of backbone atoms with other atoms in the backbone or side chains. (ex: phi= 90, psi=-90 disfavoured)
Ramachandran plot
A Ramachandran plot (mapa de densidade) shows the distribution of phi and psi dihedral angles that are found in a protein:
• shows the common secondary structure elements
• reveals regions with unusual backbone structure
Secondary Structures
Secondary structure is the 3D structure formed by hydrogen bonds between peptide NH and CO groups of amino acids that are near one another in the primary structure.
Two regular arrangements are common
• the alpha helix stabilized by hydrogen bonds between nearby residues
• the beta sheet stabilized by hydrogen bonds between adjacent segments that may not be nearby
Irregular arrangement of the polypeptide chain is called the random coil.
The alpha helix
• Helical backbone is held together by hydrogen bonds between the backbone amides of an n and n + 4 amino acids (In the α helix, the CO group of residue i forms a hydrogen bond with the NH group of residue I + 4)
• It is a right-handed helix with 3.6 residues (5.4 Å) per turn (essentially all α helices in proteins are right-handed)
• Peptide bonds are aligned roughly parallel with the helical axis.
• Side chains point out and are roughly perpendicular with the helical axis.
Amino acids #1 and #8 align nicely on top of each other.
The inner diameter of the helix (no side chains) is about 4–5 Å- too small for anything to fit “inside”
The outer diameter of the helix (with side chains)is 10–12Å.- Happens to fit well into the major groove of dsDNA
Sequence Affects Helix Stability
- Not all polypeptide sequences adopt alpha-helical structures.
- Small hydrophobic residues such as Ala and Leu are strong helix formers.
- Pro acts as a helix breaker because the rotation around the N-Calpha (φ-angle) bond is impossible.
- Gly acts as a helix breaker because the tiny R group supports other conformations.
- Attractive or repulsive interactions between side chains 3 to 4 amino acids apart will affect formation.
The Helix Dipole
- Recall that the peptide bond has a strong dipole moment.
- C−O (carbonyl) negative
- N−H (amide) positive
- All peptide bonds int he alpha helix have a similar orientation.
- The alpha helix has a large macroscopic dipole moment that is enhanced by unpaired amides and carbonyls near the ends of the helix.
- Negatively charged residues often occur near the positive end of the helix dipole.
beta sheets
- The planarity of the peptide bond and tetrahedral geometry of the alpha carbon create a pleated sheet-like structure! (Resulta das caraterísticas planares da cadeia polipeptídica)
- Sheet-like arrangement of the backbone is held together by hydrogen bonds between the backbone amides in different strands.
- Side chains protrude from the sheet, alternating in an up-and- down direction.
- antiparallel
- parallel
- mixed
An antiparallel β sheet
Adjacent β strands run in opposite directions.
Hydrogen bonds between NH and CO groups connect each amino acid to a single amino acid on an adjacent strand, stabilizing the structure. Hydrogen bonds between strands are linear (stronger)
A parallel β sheet
Adjacent β strands run in the same direction
Hydrogen bonds connect each amino acid on one strand with two different amino acids on the adjacent strand. Hydrogen bonds between strands are bent (weaker).
Beta Turns
- β turns occur frequently whenever strands in β sheets change the direction.
- The 180 turn is 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 (interação do backbone! Não da cadeia lateral!)
- Proline in position 2 (type I β turn: occurs more than twice as frequently as type II) or glycine in position 3 (type II β turn)
Protein Tertiary Structure
Tertiary structure refers to the overall spatial arrangement of atoms in a protein.
The tertiary structure of a protein is the 3-dimensional shape of the protein chain. This shape is determined by the characteristics of the AA making up the chain.
Favorable Interactions in Proteins
Stabilized by numerous weak interactions between AA side chains:
Hydrophobic interactions (reorganização da cadeia peptídica --> AA apolares no interior) Hydrogen bonds London dispersion Electrostatic interactions
Interacting AA are not necessarily next to each other in the primary sequence
Major classes of Proteins
2: fibrous & globular
Fibrous proteins
In fibrous proteins the fundamental structural unit is a simple repeating element of secondary structure. (–> Proteínas fibrosas resultam da repetição de uma unidade estrutural secundária.)
insoluble in water (because of high number of interior/surface hydrophobic residues–> força de coesão –> resistência)
hydrophobic surfaces are buried by packing many similar polypeptide chains into elaborate supramolecular complexes
Ex:
• Collagen
• Keratin
• Silk Fibroin
