The C alpha-H center dot center dot center dot O hydrogen bond: A determinant of stability and specificity in transmembrane helix interactions

The C alpha -(HO)-O-... hydrogen bond has been given Tittle attention as a determinant of transmembrane helix association. Stimulated by recent calcul ations suggesting that such bonds can be much stronger than has been suppos ed, we have analyzed 11 known membrane protein structures and found that ap parent carbon hydrogen bonds cluster frequently at glycine-, serine-, and t hreonine-rich packing interfaces between transmembrane helices. Parallel ri ght-handed helix-helix interactions appear to favor C alpha -(HO)-O-... bon d formation. In particular, C alpha -(HO)-O-... interactions are frequent b etween helices having the structural motif of the glycophorin A dieter and the GxxxG pair. We suggest that C alpha -(HO)-O-... hydrogen bonds are impo rtant determinants of stability and, depending on packing, specificity in m embrane protein folding.