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Intrahelical hydrogen bonding of serine, threonine and cysteine residues within α-helices and its relevance to membrane-bound proteins

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Abstract

A survey of known protein structures reveals that approximately 70% of serine residues and at least 85% (potentially 100%) of threonine residues in helices make hydrogen bonds to carbonyl oxygen atoms in the preceding turn of the helix. The high frequency of intrahelical hydrogen bonding is of particular significance for intrinsic membrane-bound proteins that form transmembrane helices. Hydrogen bonding within a helix provides a way for serine, threonine and cysteine residues to satisfy their hydrogen-bonding potential, permitting such residues to occur in helices buried within a hydrophobic milieu.

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      Citation Excerpt :

      Such a carboxylate-hydroxyl H-bond motif could couple protonation change to changes in local helix dynamics, which can then propagate to remote regions of the protein: The protonation state of the carboxylate group impacts the strength of its inter-helical H-bond to the Ser/Thr hydroxyl group, which in turn influences the availability of the hydroxyl group to engage in intra-helical H-bonding to a backbone carbonyl group (Bondar & Smith, 2017). Intra-helical H-bonding of Ser/Thr to the i-4 backbone carbonyl group of the preceding helical turn is common in α-helical proteins, as it lowers the energetic cost associated with inserting the hydrophilic sidechain into the membrane (Gray & Matthews, 1984). Depending on the sequence-structure context, intra-helical H-bonding between a Ser/Thr hydroxyl and a protein backbone group can associate with enhanced local dynamics of the helix, or with enhanced local hydration (del Val et al., 2012).

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    The work was supported in part by grants from the National Institutes of Health (GM20066; GM21967), the National Science Foundation (PCM-8014311) and the M. J. Murdock Charitable Trust. T.M.G. was supported by an NSF graduate fellowship.

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