BACK TO DISCOVER
Secondary Structure
Secondary structure refers to the local, spatial organization of peptide backbones stabilized primarily by hydrogen bonding between the amide hydrogen (–NH) and carbonyl oxygen (–C=O) groups of the peptide bond. Unlike the primary sequence, which is linear, secondary structures provide the first level of 3D folding and serve as the basis for higher-order tertiary and quaternary structures.
The α-Helix
Proposed by Linus Pauling and Robert Corey (1951).
Right-handed helix with:
3.6 amino acid residues per turn
5.4 Å pitch per turn
Stabilized by intrachain hydrogen bonds between the carbonyl oxygen of residue i and the amide hydrogen of residue i+4.
Side chains project outward and slightly downward, reducing steric clashes.
Often found in globular proteins, DNA-binding motifs (helix-turn-helix, leucine zippers), and membrane-spanning regions of proteins.
Destabilizing residues: Proline (helix breaker), Glycine (too flexible).
The β-Sheet
Comprised of extended β-strands that align side by side.
Stabilized by hydrogen bonds between backbone atoms of adjacent strands.
Arrangements:
Parallel β-sheets: strands run in the same direction; H-bonds angled, less stable.
Antiparallel β-sheets: strands run in opposite directions; H-bonds linear, more stable.
Side chains alternate above and below the plane of the sheet.
Structural roles: form β-barrels in membrane channels, fibrous proteins, and pathological aggregates (e.g., amyloid fibrils).
The β-Turn and Loops
β-turns allow abrupt changes in direction of the peptide chain.
Stabilized by an H-bond between residue i and i+3.
Frequently involve glycine (flexibility) and proline (rigidity).
Loops are irregular, non-repetitive structures that connect α-helices and β-sheets.
Often found at the protein surface.
Play critical roles in enzyme active sites and antibody antigen-binding regions (CDRs).
Other Helical Motifs
310 helix: tighter than α-helix, with 3 residues per turn.
π-helix: looser, with ~4.4 residues per turn; rare but found in ligand-binding sites.
Polyproline helix: left-handed extended helix typical in collagen and structural proteins.
Stabilizing Factors
Hydrogen bonds between backbone atoms (main stabilizer).
Steric effects: bulky or conformationally restricted residues influence formation.
Electrostatic interactions: the α-helix exhibits a macrodipole with partial positive charge at the N-terminus and partial negative at the C-terminus.
Hydrophobic interactions: packing of helices and sheets in tertiary structures.
Secondary structure refers to the local, spatial organization of peptide backbones stabilized primarily by hydrogen bonding between the amide hydrogen (–NH) and carbonyl oxygen (–C=O) groups of the peptide bond. Unlike the primary sequence, which is linear, secondary structures provide the first level of 3D folding and serve as the basis for higher-order tertiary and quaternary structures.
The α-Helix
Proposed by Linus Pauling and Robert Corey (1951).
Right-handed helix with:
3.6 amino acid residues per turn
5.4 Å pitch per turn
Stabilized by intrachain hydrogen bonds between the carbonyl oxygen of residue i and the amide hydrogen of residue i+4.
Side chains project outward and slightly downward, reducing steric clashes.
Often found in globular proteins, DNA-binding motifs (helix-turn-helix, leucine zippers), and membrane-spanning regions of proteins.
Destabilizing residues: Proline (helix breaker), Glycine (too flexible).
The β-Sheet
Comprised of extended β-strands that align side by side.
Stabilized by hydrogen bonds between backbone atoms of adjacent strands.
Arrangements:
Parallel β-sheets: strands run in the same direction; H-bonds angled, less stable.
Antiparallel β-sheets: strands run in opposite directions; H-bonds linear, more stable.
Side chains alternate above and below the plane of the sheet.
Structural roles: form β-barrels in membrane channels, fibrous proteins, and pathological aggregates (e.g., amyloid fibrils).
The β-Turn and Loops
β-turns allow abrupt changes in direction of the peptide chain.
Stabilized by an H-bond between residue i and i+3.
Frequently involve glycine (flexibility) and proline (rigidity).
Loops are irregular, non-repetitive structures that connect α-helices and β-sheets.
Often found at the protein surface.
Play critical roles in enzyme active sites and antibody antigen-binding regions (CDRs).
Other Helical Motifs
310 helix: tighter than α-helix, with 3 residues per turn.
π-helix: looser, with ~4.4 residues per turn; rare but found in ligand-binding sites.
Polyproline helix: left-handed extended helix typical in collagen and structural proteins.
Stabilizing Factors
Hydrogen bonds between backbone atoms (main stabilizer).
Steric effects: bulky or conformationally restricted residues influence formation.
Electrostatic interactions: the α-helix exhibits a macrodipole with partial positive charge at the N-terminus and partial negative at the C-terminus.
Hydrophobic interactions: packing of helices and sheets in tertiary structures.