Alpha helix

From Proteopedia

An is a type of secondary structure, i.e. a description of how the main chain of a protein is arranged in space. It is a repetitive regular secondary structure (just like the beta strand), i.e. all residues have similar conformation and hydrogen bonding, and it can be of arbitrary length.

Structure, hydrogen bonding and composition

Types of proteins and folds that contain alpha helices

Alpha helices in soluble (globular) proteins

The first two protein structures to be determined, myoglobin and hemoglobin, consist mainly of alpha helices. Researchers were surprised to see how random the orientation of helices seemed to be. Other all alpha-helical proteins show bundles of nearly parallel (or antiparallel) helices (e.g. bacterial cytochrome c' 1e83). In structures that have beta sheets and alpha helices, one common fold is a single beta sheet that is sandwiched by layers of alpha helices on either side (for example Carboxypeptidase A). When an alpha helix runs along the surface of the protein, one side of it will show polar side chains (solvent accessible) while the other side will show non-polar side chains (part of the hydrophobic core). The alpha helix fits nicely into the major groove of DNA. Many common DNA-binding motifs, such as the helix-turn-helix (e.g. FIS protein) or the zinc finger motif (e.g. engineered zinc finger protein 2i13), feature a short alpha helix that binds to the major groove of DNA.

Alpha helices in transmembrane proteins

A common fold found in transmembrane proteins are alpha-helical bundles running from one side to the other side of the membrane. An alpha helix of 19 amino acids (with a length of about 30 angstroms) has the right size to cross the double-layer of a typical membrane. If the helix runs at an angle instead of perfectly perpendicular to the membrane, it has to be a bit longer. There is a write-up on opioid receptors that illustrates this fold in the Molecule of the Month series by David Goodsell (http://pdb101.rcsb.org/motm/217).

Alpha helices in coiled coils

Alpha helices are named after alpha keratin, a fibrous protein consisting of two alpha helices twisted around each other in a coiled-coil (see Coiled coil). In leucine zipper proteins (such as Gcn4), the ends of the two alpha helices bind to two opposite major grooves of DNA. The name leucine zipper comes from the regularly spaced leucine side chains from both helices that form the hydrophobic core of these structures. The structure of collagen, the most abundant human protein, is also fibrous, but it is not made up of alpha helices.

Experimental evidence

There are multiple spectroscopic techniques that allow the detection of alpha helices in proteins without determining their three-dimensional structures

a) CD spectroscopy This method uses the so-called circular dichroism (CD) of proteins to estimate the content of alpha helical segments in a sample. The CD effect works because proteins are chiral (they and their mirror image are different, just like our hands). Depending on the conformation of the main chain, different spectra characteristic for alpha helices or other secondary structures are observed. For more information, take a look at the Birkbeck's PPS2 course. In a similar way, infrared spectroscopy can be used to estimate alpha helical content.

b) NMR chemical shifts Nuclear magnetic resonance spectroscopy measures magnetic properties of the nuclei of atoms. One of these properties, the so-called chemical shift, changes slightly depending on the chemical environment an atom is in. By measuring the chemical shift of the alpha and beta carbon in each amino acid residue, it is possible to predict the secondary structure the residue is part of.

Role of alpha helices in the history of structural biology

a) While the chemical (primary) structure of proteins was known for some time, the conformation of proteins was not known until the first protein structures were solved by X-ray crystallography in 1958 (myoglobin) and in the 1960s. However, using the X-ray diffraction pattern of alpha keratin (found, for example, in horse hair) and chemical insight gained from structures of smaller molecules (e.g. the peptide plane resulting from the partial double bond character of the peptide bond, the geometry of hydrogen bonds), Pauling predicted the structure of the alpha helix correctly years earlier (paper1 and paper2 and picture.

b) Determination of hand: There are several methods in X-ray crystallography where crystallographers obtain an electron density, but don't know whether it or its mirror image is correct. Historically, finding electron density that fits a helix was used to break this ambiguity. If the helix was right-handed, the electron density was used as is, but if the helix was left-handed, the mirror image was used.

c) Tracing the chain: When building a model into electron density, the first step was to place contiguous C-alpha atoms into the density (with proper spacing). To see in which direction an alpha helix goes, you look at the side chain density. If it points up, the N-terminus is on top, otherwise on the bottom. (search for Christmas tree in this course)

Quiz

See Also

• Helices in Proteins: alpha, 3₁₀, and pi helices side by side.
• Proteins: primary and secondary structure
• Secondary structure
• Protein primary, secondary, tertiary and quaternary structure / Estructuras primaria, secundaria, terciaria y cuaternaria de las proteínas
• Introduction to molecular visualization

References