ST staple is a structural motif found in proteins and polypeptides, named for the amino acids serine (Ser, S) and threonine (Thr, T), which occupy its C-terminal position. The motif comprises four or five consecutive amino acid residues and is defined by a single hydrogen bond between the side-chain hydroxyl group of the terminal serine or threonine and the main-chain carbonyl group of the first residue of the motif (designated residue i). The hydrogen-bonding partner lies at position i + 3 in the four-residue form and i + 4 in the five-residue form.
Definition and geometry
According to the Motif Glossary maintained in association with the work of E. J. Milner-White and colleagues, an ST staple consists of four or five consecutive residues and one hydrogen bond, subject to the following conditions:
- Serine or threonine is present at the final residue (position −4 or −5).
- A hydrogen bond exists between the side-chain OH of that final residue and the main-chain CO of residue −1.
- The residues not directly involved in hydrogen bonding occupy the αR (right-handed α-helical) conformation.
Sub-categories distinguish serine-containing staples from threonine-containing staples for each of the four-residue and five-residue variants. The glossary notes that its current formulation differs slightly from earlier definitions by explicitly restricting the inner residues to the αR conformation, thereby excluding the βR conformation.
Context within protein structure
Most ST staples occur in association with an α-helix and are usually accompanied by a slight bend in the helix. Because the serine or threonine side chain links the main chain of one helical turn to that of an adjacent turn, the motif has been described as effectively "stapling" two neighbouring turns of an α-helix together — the origin of the term "staple." In the five-residue variant, the requirement for an αR conformation in the intervening residues means that a second, main-chain hydrogen bond (between the NH of residue −5 and the CO of residue −1) is almost invariably present as well.
Background literature
The motif is related to early observations on side-chain–main-chain hydrogen bonding within α-helices. Gray and Matthews (1984) reported that a large majority of serine and threonine residues in helices hydrogen-bond to carbonyl oxygen atoms in the preceding turn of the helix, and discussed the relevance of such intrahelical bonding to membrane-bound proteins. Ballesteros and Deupi (2000) subsequently described how serine and threonine residues in the χ1 g− conformation bend α-helices. Databases and web tools for locating and examining such small three-dimensional motifs include Motivated Proteins (Leader and Milner-White, 2009) and PDBeMotif/MSDmotif (Golovin and Henrick, 2008).
Relationship to other terms
The ST staple is listed among protein structural motifs and is distinct from, though related to, the broader categories of the ST motif, the ST turn, and other small hydrogen-bonded motifs catalogued in the same glossaries and databases.
References
- Gray, T. M.; Matthews, B. W. (1984). "Intrahelical hydrogen bonding of serine, threonine and cysteine residues within α-helices. Relevance to membrane-bound proteins." Journal of Molecular Biology 175 (1): 75–82. doi:10.1016/0022-2836(84)90446-7. PMID 6427470.
- Ballesteros, J. A.; Deupi, X. (2000). "Serine and threonine residues bend alpha-helices in the chi(1) 5 g(-) conformation." Biophysical Journal 79 (5): 2754–2760. doi:10.1016/S0006-3495(00)76514-3. PMID 11053148.
- Leader, D. P.; Milner-White, E. J. (2009). "Motivated Proteins: A web application for studying small three-dimensional protein motifs." BMC Bioinformatics 10: 60. doi:10.1186/1471-2105-10-60. PMID 19210785.
- Golovin, A.; Henrick, K. (2008). "MSDmotif: exploring protein sites and motifs." BMC Bioinformatics 9: 312. doi:10.1186/1471-2105-9-312. PMID 18637174.
- Motif Glossary, ST Staple (reference cited therein: Milner-White, unpublished).
