Interhelical hydrogen bonds and spatial motifs in membrane proteins: Polar clamps and serine zippers

Polar and ionizable amino acid residues are frequently found in the transmembrane (TM) regions of membrane proteins. In this study, we show that they help to form extensive hydrogen bond connections between TM helices. We find that almost all TM helices have interhelical hydrogen bonding. In addition, we find that a pair of contacting TM helices is packed tighter when there are interhelical hydrogen bonds between them. We further describe several spatial motifs in the TM regions, including “Polar Clamp” and “Serine Zipper,” where conserved Ser residues coincide with tightly packed locations in the TM region. With the examples of halorhodopsin, calcium‐transporting ATPase, and bovine cytochrome c oxidase, we discuss the roles of hydrogen bonds in stabilizing helical bundles in polytopic membrane proteins and in protein functions. Proteins 2002;47:209–218. © 2002 Wiley‐Liss, Inc.

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