BAR Domains Amphipathic Helices

There is another major way in which proteins can bend membranes. It is possible for proteins that penetrate the membrane to occupy the leaflets asymmetrically, expanding one leaflet at the expense of the other. A well-studied example is the reversible association between membranes and proteins containing a so-called 'amphipathic helix'. The idea here is that the protein adopts a helical secondary structure (a common conformation) but the amino acid sequence of this helix is such that one side of the cylindrical structure is hydrophobic, and therefore naturally associates with the membrane, while the other side is hydrophilic, and does not. This protein can therefore embed in the surface of the membrane to which it is presented (typically cytosolic), and expand that surface, typically bending the membrane inwards at that point (Fig. 3d).

This motif is often associated with a curved banana-shaped strut-type structure known as a BAR (bin, amphiphysin Rvs) domain [17], whose crystal structure was elucidated by the McMahon lab [25, 47]. This domain is found in many different proteins (amphiphysin, endophilins, BRAP1/bin2, nadrins, tuba, oligophrenin, centaurin, nexins, and arfaptins) but none of these has ever been associated with the red cell [46]. However, other proteins that have an amphiphilic helix could be hard to find. This is a structural feature rather than a sequence feature. It requires two characteristics, first that the protein adopts a helical structure, and second that one side of the helix is hydrophobic and the other hydrophilic. It can be imagined that many proteins could fulfil this condition; they need have no sequence similarity to those that are already characterised, simply that roughly every third amino acid should be hydrophobic in character.

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