Alpha helix

Structure and hydrogen bondingStructure and hydrogen bonding

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 from amino acid n to n+4. There are . If you , you can see how 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 (https://www.ncbi.nlm.nih.gov/books/NBK22580/figure/A322/?report=objectonly).] Apart from the characteristic hydrogen bonding patters, the other identifying feature of alpha helices are the main chain torsion angles phi and psi. 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, see Ramachandran Plot or http://www.cryst.bbk.ac.uk/PPS95/course/3_geometry/rama.html. Which amino acids are found in alpha helices? Proline is a helix breaker because its main chain nitrogen is not available for hydrogen bonding. Amino acid side chains whose movement is largely restricted in an alpha helix (branched at beta carbon like threonine or valine) are disfavored, as is glycine. Here is an example of a at the position of a . Prolines are often found at 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).

spinqualitylabelsall models alpha helix Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Types of proteins and folds that contain alpha helicesTypes of proteins and folds that contain alpha helices

Alpha helices in soluble (globular) proteinsAlpha helices in soluble (globular) proteins

Example: myoglobin Example: helical DNA binding domains

Alpha helices in transmembrane proteinsAlpha 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 coilsAlpha helices in coiled coils

Coiled coil Gcn4

Experimental evidenceExperimental evidence

a) CD spectroscopy http://www.cryst.bbk.ac.uk/PPS2/course/section8/ss-960531_21.html

b) NMR chemical shifts

Role of alpha helices in the history of structural biologyRole of alpha helices in the history of structural biology

a) Pauling predicts it http://onlinelibrary.wiley.com/doi/10.1111/febs.12796/full

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 http://www-structmed.cimr.cam.ac.uk/Course/Fitting/fittingtalk.html)