The alpha helix, or α-helix, is a regular, usually right-handed arrangement of the backbone of a protein. It is one of the principal forms of protein secondary structure, alongside the beta sheet. Its defining feature is a repeating pattern of hydrogen bonds between backbone groups separated by four amino acid residues in the sequence. Secondary structure describes local backbone organization rather than the complete three-dimensional shape of a protein. (ebi.ac.uk)
Backbone geometry
A polypeptide chain consists of amino acid residues joined by peptide bonds. In an ideal alpha helix, successive residues follow the same repeating conformation, producing approximately 3.6 residues per turn. Each residue advances about 1.5 ångströms along the helix axis, giving a pitch—the axial distance covered by one complete turn—of approximately 5.4 ångströms. Side chains project outward, leaving the backbone to form the central helical framework. These dimensions describe an idealized structure; helices in proteins can deviate from perfect regularity. (ebi.ac.uk)
Handedness is related to amino acid chirality. The L-amino acids that predominate in naturally synthesized proteins generally favor right-handed alpha helices because this arrangement reduces unfavorable interference between side chains and the backbone. A left-handed alpha helix is geometrically possible, but it is not the usual configuration in proteins. The designation “L-amino acid” therefore does not imply a left-handed protein helix. (ebi.ac.uk)
Backbone conformation can also be described by two torsion angles, conventionally called φ and ψ. A Ramachandran plot displays their combinations and identifies regions compatible with particular secondary structures. Repeated placement of consecutive residues in the alpha-helical region is characteristic of a helix, although backbone angles alone do not describe every aspect of its hydrogen-bonding network. (ebi.ac.uk)
Hydrogen bonding and helix ends
The characteristic interaction joins the carbonyl oxygen of residue i to the backbone N–H group of residue i + 4. The carbonyl group accepts the hydrogen bond, while the N–H group donates it. Thus, the bonds involve the backbone rather than requiring particular side chains. This distinction explains why many different amino acid sequences can adopt the same helical structure. (rcsb.org)
The repeating network cannot continue unchanged at the ends of a finite helix. Near the N-terminal end, some backbone N–H groups lack their usual partners within the helix; near the C-terminal end, some carbonyl groups lack theirs. Helix capping describes local arrangements that help accommodate these groups, including hydrogen bonds with neighboring side chains or backbone segments. Capping motifs contribute to the preference for particular residues at helix boundaries. (pmc.ncbi.nlm.nih.gov)
The ordered peptide groups also produce an electrostatic effect often described as a helix dipole, related to an electric dipole. Its ends have partial positive character toward the N terminus and partial negative character toward the C terminus. The resulting interactions depend on residue position and the surrounding protein environment; their contribution cannot be represented by a single universal stabilization value. (pmc.ncbi.nlm.nih.gov)
Sequence preferences and stability
Amino acids differ in their helix propensity, meaning their tendency to favor the alpha-helical conformation under specified conditions. Experimental comparisons commonly identify alanine as a strong helix former and glycine as relatively unfavorable. Glycine has unusually broad conformational freedom, so restricting it to a regular helix carries a larger conformational entropy cost. Propensity scales are useful, but they do not determine structure independently of sequence context. (pubmed.ncbi.nlm.nih.gov)
Proline is distinctive because its side chain closes a ring with the backbone nitrogen. An internal proline residue lacks the ordinary backbone N–H donor and often produces a bend or interruption in a helix. Nevertheless, “helix breaker” is not an absolute prohibition: experiments show that proline’s effects vary substantially between aqueous and membrane-like environments. (ebi.ac.uk)
Helix formation is part of protein folding, and stability depends on interactions within the helix and with the rest of the protein. Experiments comparing isolated peptides with intact proteins have found close agreement in helix propensities in favorable cases, demonstrating both the usefulness of peptide models and the importance of specifying their context. (pmc.ncbi.nlm.nih.gov)
Roles in protein architecture
Alpha helices provide compact structural elements that can pack into larger protein folds. In myoglobin, helices assemble into a globular structure, with carbon-rich side chains largely sheltered from surrounding water and charged residues commonly exposed at the surface. This illustrates how local secondary structure combines with side-chain organization to produce a folded protein. (pdb101.rcsb.org)
Helices also frequently span the lipid bilayer of a cell membrane. Their compact axial rise allows a segment of roughly twenty residues to extend about thirty ångströms. This makes the alpha helix a suitable structural unit for many membrane-spanning proteins. (ebi.ac.uk)
Experimental identification
Atomic structures obtained through X-ray crystallography, nuclear magnetic resonance, and electron microscopy allow researchers to examine protein backbone organization. Helices can be assessed through their geometry and hydrogen-bonding pattern rather than merely through the appearance of a spiral in a molecular illustration. (pdb101.rcsb.org)
Circular dichroism provides a complementary spectroscopic measurement of helical structure in solution. Alpha-helical peptides characteristically show negative bands near 208 and 222 nanometres. Measurements at 222 nanometres are widely used in experiments comparing peptide helicity and helix-forming tendencies. (pmc.ncbi.nlm.nih.gov)
Historical development
Linus Pauling, Robert B. Corey, and Herman R. Branson proposed the alpha-helical configuration in a paper published in April 1951. Their model used experimentally established interatomic distances, bond angles, the planar peptide group, and plausible hydrogen bonds to construct repeating polypeptide conformations. The paper identified a helix with approximately 3.7 residues per turn as a likely structural feature of both fibrous and globular proteins, anticipating the central role subsequently established for alpha helices. (pubmed.ncbi.nlm.nih.gov)