Alpha helix

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Contents 1 Structure, hydrogen bonding and composition 2 Types of proteins and folds that contain alpha helices 2.1 Alpha helices in soluble (globular) proteins 2.2 Alpha helices in transmembrane proteins 2.3 Alpha helices in coiled coils 3 Experimental evidence 4 Role of alpha helices in the history of structural biology 5 References

Structure, hydrogen bonding and composition

spinqualitylabelsall models alpha helix Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image An alpha helix 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. In an alpha helix, the main chain arranges in a with the side chains (green) pointing away from the helical axis. The alpha helix is stabilized by (shown as dashed lines) from the carbonyl group of one amino acid to the amino group of a second amino acid. Because the amino acids connected by each hydrogen bond are four apart in the primary sequence, these main chain hydrogen bonds are called "n to n+4". There are . If you to a Spacefilling representation, you can see how tightly packed the main chain is (no space in the middle). [The previous scenes were inspired by a beautiful set of figures in Stryer's biochemistry textbook.] Apart from the characteristic hydrogen bonding patters, the other identifying feature of alpha helices are the main chain torsion angles . If you plot phi against psi for each residue (so-called Ramachandran plot), you find that the phi/psi combination found in alpha helices fall into one of the three "allowed" (i.e. observed) areas for non-glycine residues. For a more detailed explanation with examples of Ramachandran plots, see Ramachandran Plot or Birkbeck's PPS95 course. Which amino acids are found in alpha helices? Some amino acids are commonly found in alpha helices and others are rare. Knowing the so-called helix propensities, it is possible to predict where helices occur in a protein sequence. Amino acids with a side chain whose movement is largely restricted in an alpha helix (branched at beta carbon like threonine or valine) are disfavored, i.e. occur less often in alpha helices than in other secondary structure elements. Glycine, with its many possible main chain conformations, is also rarely found in helices. Proline is considered a helix breaker because its main chain nitrogen is not available for hydrogen bonding. Here is an example of a at the position of a . Prolines are often found near the beginning or end of an alpha helix, as in this example of (this is an ultra high resolution structure where hydrogen atoms - white - are resolved and some atoms are shown in multiple positions). At the of the helix, there is a proline that interrupts the regular pattern of n to n+4 hydrogen bonds. Instead, the helix ends with an n to n+3 hydrogen bond (one turn of a so-called 3-10 helix, see Helices in Proteins). The subsequent proline is in the center of a turn, followed by a glycine (which is part of an n to n+3 hydrogen bond also typical for turns). The beginnings and ends of helices are called N-caps and C-caps, respectively, and they have interesting sequence and structural patterns involving main chain or side chain hydrogen bonding.

Types of proteins and folds that contain alpha helices

Alpha helices in soluble (globular) proteins

Example: myoglobin Example: helical DNA binding domains

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 receptiors 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

Coiled coil Gcn4

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)

References