A unified hydrophobicity scale for multispan membrane proteins
A unified hydrophobicity scale for multispan membrane proteins
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DOI：
10.1002/prot.22315
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发表时间：
2009-07-01
影响因子：
2.9
通讯作者：
Meiler, Jens
中科院分区：
文献类型：
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作者：
Koehler, Julia;Woetzel, Nils;Meiler, Jens
疏水性的概念对于我们理解膜蛋白 (MP) 折叠、结构和功能的原理至关重要。在过去的几十年中，一些研究小组使用实验和统计方法得出了疏水性尺度，这些方法经过优化以尽可能接近地模拟某些自然现象。目前的工作为该工具集添加了第一个基于知识的量表，该量表统一了 a 螺旋和 beta 桶多跨 MP 的特征。这种统一的疏水性尺度 (UHS) 区分了氨基酸对溶液、过渡和跨膜状态的偏好。该比例代表折叠蛋白质中氨基酸的平均疏水性值，无论其二级结构类型如何。我们还提出了第一个基于知识的哺乳动物α螺旋MP疏水性量表（哺乳动物疏水性量表-MHS）。这两种尺度对于计算蛋白质结构阐明特别有用，例如作为机器学习技术的输入，例如二级结构或跨膜跨度预测，或作为蛋白质结构预测或蛋白质设计的参考能量。基于知识的 UHS 显示出与 Hessa 及其同事最近引入的实验疏水性量表惊人的相似性（Hessa T 等人，Nature 2007；450：U1026-UI032）。将两种截然不同的方法融合到相似的疏水性值上，巩固了早期研究中观察到的实验和基于知识的尺度之间的主要差异。此外，UHS 标度代表了折叠式多跨 MP 的精确绝对自由能测量，这是许多现有标度所不具备的功能。通过分析一系列不同的议员，证明了 UHS 的实用性。进一步表明，UHS 在预测沿蛋白质序列的跨膜跨度方面优于九个已建立的疏水性尺度。当前疏水性量表的准确性得益于过去四年 PDB 中完整 MP 数量翻倍。 UHS 为提高跨膜跨度预测的准确性铺平了道路。
The concept of hydrophobicity is critical to our understanding of the principles of membrane protein (MP) folding, structure, and function. In the last decades, several groups have derived hydrophobicity scales using both experimental and statistical methods that are optimized to mimic certain natural phenomena as closely as possible. The present work adds to this toolset the first knowledge-based scale that unifies the characteristics of both a-helical and beta-barrel multispan MPs. This unified hydrophobicity scale (UHS) distinguishes between amino acid preference for solution, transition, and trans-membrane states. The scale represents average hydrophobicity values of amino acids in folded proteins, irrespective of their secondary structure type. We furthermore present the first knowledge-based hydrophobicity scale for mammalian a-helical MPs (mammalian hydrophobicity scale-MHS). Both scales are particularly useful for computational protein structure elucidation, for example as input for machine learning techniques, such as secondary structure or trans-membrane span prediction, or as reference energies for protein structure prediction or protein design. The knowledge-based UHS shows a striking similarity to a recent experimental hydrophobicity scale introduced by Hessa and coworkers (Hessa T et al., Nature 2007;450:U1026-UI032). Convergence of two very different approaches onto similar hydrophobicity values consolidates the major differences between experimental and knowledge-based scales observed in earlier studies. Moreover, the UHS scale represents an accurate absolute free energy measure for folded, multispan MPs-a feature that is absent from many existing scales. The utility of the UHS was demonstrated by analyzing a series of diverse MPs. It is further shown that the UHS outperforms nine established hydrophobicity scales in predicting trans-membrane spans along the protein sequence. The accuracy of the present hydrophobicity scale profits from the doubling of the number of integral MPs in the PDB over the past four years. The UHS paves the way for an increased accuracy in the prediction of trans-membrane spans.