Coiled coils 9-to-5: rational de novo design of α-helical barrels with tunable oligomeric states.
Coiled coils 9-to-5: rational de novo design of α-helical barrels with tunable oligomeric states.
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DOI：
10.1039/d1sc00460c
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发表时间：
2021-05-26
期刊：
影响因子：
8.4
通讯作者：
Woolfson DN
中科院分区：
文献类型：
--
作者：
Dawson WM;Martin FJO;Rhys GG;Shelley KL;Brady RL;Woolfson DN
在水中可控和可预测地组装的线性肽的合理设计是具有挑战性的。短序列必须编码独特的靶结构并避免替代状态。然而，稳定和区分状态的非共价力很弱。尽管如此，对于α-螺旋卷曲螺旋组件，在合理的从头设计方面已经取得了相当大的进展。在这些中，名义上疏水（h）和极性（p）残基的序列重复，hpphppp，指导两亲性螺旋组装成二聚体到四聚体束。将这种模式扩展到hpphhph可以产生更大的α螺旋桶。在这里，我们表明，五聚体九聚体桶访问通过改变在一个H网站的残基。在具有四个L/I-K-E-I-A-x-Z重复序列的肽中，Z的大小从苏氨酸到丝氨酸到丙氨酸到甘氨酸逐渐减小，得到更大的寡聚体。所得α-螺旋桶的X射线晶体结构合理化了这一点：Z点的侧链直接进入螺旋界面，较小的残基允许更紧密的螺旋接触和更大的组装。肽的系统性从头设计，其形成具有内径范围的可官能化中心通道的α-螺旋桶。
The rational design of linear peptides that assemble controllably and predictably in water is challenging. Short sequences must encode unique target structures and avoid alternative states. However, the non-covalent forces that stabilize and discriminate between states are weak. Nonetheless, for α-helical coiled-coil assemblies considerable progress has been made in rational de novo design. In these, sequence repeats of nominally hydrophobic (h) and polar (p) residues, hpphppp, direct the assembly of amphipathic helices into dimeric to tetrameric bundles. Expanding this pattern to hpphhph can produce larger α-helical barrels. Here, we show that pentameric to nonameric barrels are accessed by varying the residue at one of the h sites. In peptides with four L/I–K–E–I–A–x–Z repeats, decreasing the size of Z from threonine to serine to alanine to glycine gives progressively larger oligomers. X-ray crystal structures of the resulting α-helical barrels rationalize this: side chains at Z point directly into the helical interfaces, and smaller residues allow closer helix contacts and larger assemblies. Systematic de novo design of peptides that form α-helical barrels with functionalisable central channels with a range of internal diameters.
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影响因子：
5.7
作者：
Lizatovic, Robert;Aurelius, Oskar;Andre, Ingemar
通讯作者：
Andre, Ingemar
影响因子：
56.9
作者：
HARBURY, PB;ZHANG, T;ALBER, T
通讯作者：
ALBER, T
影响因子：
6.2
作者：
Hume, Jasmin;Sun, Jennifer;Montclare, Jin Kim
通讯作者：
Montclare, Jin Kim
DOI：
10.1073/pnas.0604871103
发表时间：
2006-10-17
影响因子：
11.1
作者：
Liu, Jie;Zheng, Qi;Lu, Min
通讯作者：
Lu, Min
影响因子：
21.8
作者：
Burton, Antony J.;Thomson, Andrew R.;Woolfson, Derek N.
通讯作者：
Woolfson, Derek N.