Rucete ✏ Lehninger Principles of Biochemistry In a Nutshell
4.2 Protein Secondary Structure
This chapter introduces the local structural arrangements of polypeptide chains known as secondary structure, focusing on α helices, β conformations (including β sheets and β turns), and how these structures are determined, stabilized, and analyzed.
Definition and Types of Secondary Structure
• Secondary structure describes the local spatial arrangement of the main-chain atoms in a polypeptide, without considering side chains or overall protein folding.
• Regular secondary structures have repeating dihedral angles (ϕ and ψ), the most common being the α helix and β conformation; β turns and loops are also important.
• Regions without regular structure are often termed "random coil," but in reality, most backbones follow highly specific paths for function.
The α Helix
• The α helix is a right-handed helical structure stabilized by intrachain hydrogen bonds between the carbonyl oxygen of one peptide bond and the amide hydrogen of the fourth residue ahead.
• Each turn of the α helix extends 5.4 Å and includes 3.6 amino acid residues; R groups project outward from the helical axis.
• The α helix maximizes internal hydrogen bonding and is the most common helical structure in proteins (especially in α-keratins); about one-fourth of residues in typical proteins are found in α helices.
• Stability is affected by: (1) the intrinsic propensity of amino acids (Ala is favored, Pro and Gly are disfavored), (2) interactions between side chains three or four residues apart, (3) bulkiness of adjacent side chains, (4) the presence of Pro/Gly residues, (5) helix dipole and terminal charge effects.
• Negatively charged residues are often near the amino terminus, and positively charged residues near the carboxyl terminus, to stabilize the helix dipole.
The β Conformation and β Sheets
• The β conformation (beta strand) is an extended, zigzag arrangement; several strands side by side form β sheets (also called β-pleated sheets).
• β sheets can be antiparallel (opposite directions, with linear hydrogen bonds) or parallel (same direction, with distorted hydrogen bonds); antiparallel sheets are more common in nature.
• R groups project alternately above and below the plane of the sheet, contributing to pleated appearance and structural diversity.
β Turns and Loops
• β turns and loops connect segments of α helices and β strands, reversing chain direction and contributing to compact, globular protein folding.
• The most common is the β turn, involving four residues and a hydrogen bond between the first and fourth; types I and II are most frequent, often containing Gly or Pro.
• Turns are frequently found on protein surfaces, allowing interaction with the solvent.
• γ turns (three residues) also exist but are less common.
Dihedral Angles and the Ramachandran Plot
• Secondary structures are defined by characteristic sets of ϕ and ψ angles; not all angle combinations are possible due to steric hindrance.
• Ramachandran plots visualize the sterically allowed and forbidden regions for backbone dihedral angles; α helix and β conformation occupy specific areas on the plot.
• Glycine is an exception, able to adopt conformations forbidden to other residues due to its small size.
Circular Dichroism (CD) Spectroscopy
• CD spectroscopy measures differences in absorption of left- and right-circularly polarized light by peptide bonds in different environments.
• The technique is used to estimate the content of α helix and β conformation, to assess protein folding, and to monitor conformational changes.
• CD spectra provide a fingerprint for folded versus denatured states and allow estimation of secondary structure content in proteins.
In a Nutshell
• Secondary structure refers to local, regular arrangements of polypeptide backbone—mainly α helices and β sheets—defined by repeating dihedral angles and stabilized by hydrogen bonds.
• Formation and stability depend on the sequence and positioning of amino acids, as well as the specific interactions between residues.
• β turns and loops enable compact folding and chain reversal, increasing structural diversity in globular proteins.
• Techniques like Ramachandran plots and circular dichroism spectroscopy are essential for analyzing and predicting secondary structure in proteins.