Hydrogen-bonding and packing features of membrane proteins: functional implications

¹ Humboldt Universität Berlin
² Columbia University
³ Uni Goettingen

^* To whom correspondence should be addressed. E-mail: peter.hildebrand{at}charite.de.

Submitted on April 7, 2007
Revised on May 11, 2007
Accepted on 11 September 2007

	Abstract

The recent structural elucidation of about one dozen "channels" (in which we include transporters) has provided further evidence that these membrane proteins typically undergo large movements during function. However, it is still not well understood how these proteins achieve the necessary trade-off between stability and mobility. In order to identify specific structural properties of channels, we compared the helix-packing and hydrogen-bonding patterns of channels with those of membrane-coils; the latter is a class of membrane proteins whose structures are expected to be more rigid. We describe in detail how in channels, helix pairs are usually arranged in packing motifs with large crossing angles (||~40°), where the (small) side-chains point away from the packing core and the backbones of the two helices are in close contact. We found that this contributes to a significant enrichment of C-H---O bonds and to a packing geometry where right-handed parallel (= -40°±10) and anti-parallel (= +140°±25) arrangements are equally preferred. By sharp contrast, the interdigitation and hydrogen bonding of side-chains in helix pairs of membrane-coils results in narrowly-distributed left-handed anti-parallel arrangements with crossing angles = -160°±10 (||~20°). In addition, we show that these different helix-packing modes of the two types of membrane proteins correspond to specific hydrogen bonding patterns. In particular, in channels, three times more of the hydrogen-bonded helix pairs are found in parallel right-handed motifs than are non-hydrogen bonded helix pairs. Finally, we discuss how the presence of weak hydrogen-bonds, water-containing cavities and right-handed crossing angles may facilitate the required conformational flexibility between helix pairs of channels, while maintaining sufficient structural stability.

Key Words: channels and transporters, helix-helix interaction, hydrogen bonds, protein folding, protein function, protein packing

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