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首页> 外文期刊>Journal of Molecular Biology >INVESTIGATION OF THE STRUCTURAL COMPONENTS GOVERNING THE POLARITY-DEPENDENT REFOLDING OF A CD4-BINDING PEPTIDE FROM GP120
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INVESTIGATION OF THE STRUCTURAL COMPONENTS GOVERNING THE POLARITY-DEPENDENT REFOLDING OF A CD4-BINDING PEPTIDE FROM GP120

机译：研究GP120中与CD4结合的多肽极性依存性的结构组分的研究

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The conformational switch at the principle CD4-binding domain of gp120 from HIV1 exhibits a highly cooperative folding transition from beta-sheet to helix triggered within a very narrow range of solvent polarity. The physical basis of this folding behaviour is of interest because it is unusual and because it is closely connected with biological function, i.e. binding to the CD4 receptor. Previous work revealed two primary structural elements, an N-terminal LPCR tetrad and a tryptophan residue eight residues C-terminal to this, that were essential for the helical and for the beta-sheet conformation, respectively Attempts to construct synthetic ''switch'' domains using the characteristics so far identified produce peptides undergoing the transition at much higher polarity and involving fewer residues than the natural domain, in essence a lower stability of the beta-fold to apolar conditions. Introduction of a tryptophan residue reduced at the C-(2)-C-(3) linkage demonstrates clearly that the aromatic system of the tryptophan residue is central to beta-sheet stabilization. Residues with side-chains that might participate in electrostatic or aromatic interactions with the pi-electron system of Trp were sequentially altered to alanine. The results indicate that the ''switch'' properties of the CD4-binding domain arise from a poised tension between multiple interactions with the Trp aromatic ring stabilizing the beta-structure and the tendency of the LPCR tetrad to act as a template for a helical fold. Under polar conditions the former dominate. Lowering the polarity alters this both by weakening the aromatic interactions and by simultaneously increasing the helical propensities of the isoleucine and valine side-chains. Tryptophan seems uniquely suited to act as polarity-sensitive conformational sensor. [References: 15]
机译：来自HIV1的gp120的主要CD4结合结构域处的构象转换显示出在非常窄的溶剂极性范围内触发的从β-折叠到螺旋的高度协作的折叠过渡。这种折叠行为的物理基础是令人感兴趣的，因为它是不寻常的并且因为它与生物学功能紧密结合，即与CD4受体结合。先前的工作揭示了两个主要结构元件，一个N末端LPCR四分体和一个色氨酸残基，八个残基C末端，分别对于螺旋和β-折叠构象至关重要，试图构建合成的“开关”利用迄今鉴定出的特征的结构域产生的肽以比天然结构域高得多的极性过渡并且涉及比天然结构域更少的残基，实质上是β折叠对非极性条件的稳定性较低。引入在C-（2）-C-（3）键处还原的色氨酸残基清楚地表明，色氨酸残基的芳族系统对于β-折叠稳定至关重要。带有侧链的残基可能会参与与Trp的pi电子系统发生静电或芳香相互作用，随后被更改为丙氨酸。结果表明，CD4结合结构域的“开关”特性是由与Trp芳香环稳定β结构的多次相互作用之间的平衡张力和LPCRtetrad充当螺旋模板的趋势引起的折。在极地条件下，前者占主导地位。降低极性可以通过减弱芳香族相互作用以及同时增加异亮氨酸和缬氨酸侧链的螺旋性质来改变极性。色氨酸似乎特别适合用作极性敏感的构象传感器。 [参考：15]

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