Disulfide-Mediated β-Strand Dimers: Hyperstable β-Sheets Lacking Tertiary Interactions and Turns.
Disulfide-Mediated β-Strand Dimers: Hyperstable β-Sheets Lacking Tertiary Interactions and Turns.
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DOI：
10.1021/ja5117809
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发表时间：
2015-04-29
影响因子：
15
通讯作者：
Andersen NH
中科院分区：
文献类型：
--
作者：
Kier BL;Anderson JM;Andersen NH
半胱氨酸残基之间的二硫键对许多蛋白质的结构和折叠至关重要。然而，它们在结构肽和蛋白质设计中的作用经常局限于作为链内共价钉来加强现有结构或诱导结状构象。在β发夹中，它们在反平行链上的非氢键位置被证明有助于实现完全折叠的阳性对照。在这里，我们报告了一类新的设计β片肽二聚体与链中心二硫化物为关键元素。我们已经发现，仅仅在短肽链中间附近存在一个二硫键就足以形成一些反平行的β-片结构；添加β封盖单元和其他有利的交叉链相互作用产生超稳定片材。在成核β-片结构的形成方面，发现链中心半胱氨酸优于最佳设计的反转转弯。我们已经探索了这种技术的局限性和可能性（使用二硫化物作为薄片成核剂），我们为应用和进一步设计二硫化物系固的“无旋转”β-薄片提供了一套规则和原理。
Disulfide bonds between cysteine residues are essential to the structure and folding of many proteins. Yet their role in the design of structured peptides and proteins has frequently been limited to use as intra-chain covalent staples that reinforce existing structure or induce knot-like conformations. In beta hairpins, their placement at non-H-bonding positions across antiparallel strands has proven useful for achieving fully-folded positive controls. Here we report a new class of designed beta sheet peptide dimers with strand-central disulfides as the key element. We have found that the mere presence of a disulfide bond near the middle of a short peptide chain is sufficient to nucleate some antiparallel β-sheet structure; addition of β capping units and other favorable cross-strand interactions yield hyperstable sheets. Strand-central cystines were found to be superior to the best designed reversing turns in terms of nucleating β-sheet structure formation. We have explored the limitations and possibilities of this technique (the use of disulfides as sheet nucleators) and we provide a set of rules and rationales for the application and further design of disulfide-tethered “turnless” β-sheets.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.5
作者：
Anderson JM;Kier BL;Shcherbakov AA;Andersen NH
通讯作者：
Andersen NH
影响因子：
2.9
作者：
Eidenschink, Lisa;Kier, Brandon L.;Huggins, Kelly N. L.;Andersen, Niels H.
通讯作者：
Andersen, Niels H.
影响因子：
15
作者：
Andersen, Niels H.;Olsen, Katherine A.;Farazi, Shabnam R.
通讯作者：
Farazi, Shabnam R.
影响因子：
3.4
作者：
Deming, TJ
通讯作者：
Deming, TJ