The Role of Aromatic-Aromatic Interactions in Strand-Strand Stabilization of β-Sheets.
The Role of Aromatic-Aromatic Interactions in Strand-Strand Stabilization of β-Sheets.
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DOI：
10.1016/j.jmb.2013.06.030
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发表时间：
2013-09-23
影响因子：
5.6
通讯作者：
Gierasch, Lila M.
中科院分区：
文献类型：
--
作者：
Budyak, Ivan L.;Zhuravleva, Anastasia;Gierasch, Lila M.
长期以来，人们一直认为芳香族-芳香族相互作用在蛋白质结构、折叠和结合功能中发挥着关键作用。然而，我们仍然缺乏对芳香-芳香相互作用对蛋白质稳定性的贡献以及它们在折叠过程中形成的时间的充分了解。在这里，以 β-桶蛋白、细胞视黄酸结合蛋白 1 (CRABP1) 中的芳香梯为案例研究，我们发现芳香族 π 堆积在 Phe65-Phe71 交叉链对中发挥更大作用，而在另一对 Phe50-Phe65 中，疏水相互作用占主导地位。 Phe65/Phe71 对跨越 β-桶中的 β-链 4 和 5，缺乏链间氢键，我们推测它在能量上补偿了链-链主链相互作用的缺失。通过扰动分析，我们发现两个芳香族-芳香族对都是在 CRABP1 折叠的过渡态之后形成的，因此在 β-折叠的最终稳定中发挥作用，而不是像之前提出的那样在其成核中发挥作用。 CRABP1 中 4-5 链之间的芳香族相互作用在细胞内脂质结合蛋白 (iLBP) 家族中高度保守，多条证据结合起来支持一个模型，其中它起到维持桶结构的作用，同时允许配体进入所需的动态打开。最后，我们进行了生物信息学分析，发现了 51 个 iLBP 外非氢键 β 链芳香族-芳香族相互作用的例子，论证了该结构基序所起作用的普遍性。
Aromatic-aromatic interactions have long been believed to play key roles in protein structure, folding, and binding functions. Yet we still lack full understanding of the contributions of aromatic-aromatic interactions to protein stability and the timing of their formation during folding. Here, using as a case study an aromatic ladder in the β-barrel protein, cellular retinoic acid binding protein 1 (CRABP1), we find aromatic π stacking plays a greater role in the Phe65-Phe71 cross-strand pair while in another pair, Phe50-Phe65, hydrophobic interactions are dominant. The Phe65/Phe71 pair spans β-strands 4 and 5 in the β-barrel, which lack interstrand hydrogen bonding, and we speculate that it compensates energetically for the absence of strand-strand backbone interactions. Using perturbation analysis, we find that both aromatic-aromatic pairs form after the transition state for folding of CRABP1, thus playing a role in the final stabilization of the β-sheet rather than in its nucleation as had been earlier proposed. The aromatic interaction between strands 4–5 in CRABP1 is highly conserved in the intracellular lipid-binding protein (iLBP) family, and several lines of evidence combine to support a model wherein it acts to maintain barrel structure while allowing the dynamic opening that is necessary for ligand entry. Lastly, we carried out a bioinformatic analysis and found 51 examples of aromatic-aromatic interactions across non-hydrogen-bonded β-strands outside the iLBPs, arguing for the generality of the role played by this structural motif.
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影响因子：
8
作者：
Bemporad, F;Taddei, N;Chiti, F
通讯作者：
Chiti, F
DOI：
10.1111/j.1432-1033.1976.tb10390.x
发表时间：
1976-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
COGAN, U;KOPELMAN, M;SHINITZKY, M
通讯作者：
SHINITZKY, M
影响因子：
2.9
作者：
Creamer, TP;Srinivasan, R;Rose, GD
通讯作者：
Rose, GD
影响因子：
8
作者：
Betts, S;Haase-Pettingell, C;King, J
通讯作者：
King, J
影响因子：
2.7
作者：
DELAGLIO, F;GRZESIEK, S;BAX, A
通讯作者：
BAX, A