Helix packing in polytopic membrane proteins: Role of glycine in transmembrane helix association

The nature and distribution of amino acids in the helix interfaces of four polytopic membrane proteins (cytochrome c oxidase, bacteriorhodopsin, the p hotosynthetic reaction center of Rhodobacter sphaeroides, and the potassium channel of Streptomyces lividans) are studied to address the role of glyci ne in transmembrane helix packing. In contrast to soluble proteins where gl ycine is a noted helix breaker, the backbone dihedral angles of glycine in transmembrane helices largely fall in the standard a-helical region of a Ra machandran plot. An analysis of helix packing reveals that glycine residues in the transmembrane region of these proteins are predominantly oriented t oward helix-helix interfaces and have a high occurrence at helix crossing p oints. Moreover, packing Voids are generally not formed at the position of glycine in folded protein structures. This suggests that transmembrane glyc ine residues mediate helix-helix interactions in polytopic membrane protein s in a fashion similar to that seen in oligomers of membrane proteins with single membrane-spanning helices. The picture that emerges is one where gly cine residues serve as molecular notches for orienting multiple helices in a folded protein complex.