Yuan X, Werner J M, Knott V, Handford P A, Campbell I D, Downing K
Department of Biochemistry, University of Oxford, United Kingdom.
Protein Sci. 1998 Oct;7(10):2127-35. doi: 10.1002/pro.5560071009.
The transforming growth factor beta (TGF-beta) binding protein-like (TB) domain is found principally in proteins localized to extracellular matrix fibrils, including human fibrillin-1, the defective protein in the Marfan syndrome. Analysis of the nuclear magnetic resonance (NMR) data for the sixth TB module from human fibrillin-1 has revealed the existence of two stable conformers that differ in the isomerization states of two proline residues. Unusually, the two isoforms do not readily interconvert and are stable on the time scale of milliseconds. We have computed independent structures of the major and minor conformers of TB6 to assess how the domain fold adjusts to incorporate alternatively cis- or trans-prolines. Based on previous observations, it has been suggested that multiple conformers can only be accommodated in flexible regions of protein structure. In contrast, P22, which exists in trans in the major form and cis in the minor form of TB6, is in a rigid region of the domain, which is confirmed by backbone dynamics measurements. Overall, the structures of the major and minor conformers are similar. However, the secondary structure topologies of the two forms differ as a direct consequence of the changes in proline conformation.
转化生长因子β（TGF-β）结合蛋白样（TB）结构域主要存在于定位于细胞外基质原纤维的蛋白质中，包括人原纤蛋白-1，它是马凡综合征中的缺陷蛋白。对人原纤蛋白-1第六个TB模块的核磁共振（NMR）数据的分析揭示了存在两种稳定的构象异构体，它们在两个脯氨酸残基的异构化状态上有所不同。不同寻常的是，这两种异构体不易相互转化，并且在毫秒时间尺度上是稳定的。我们已经计算了TB6主要和次要构象异构体的独立结构，以评估该结构域折叠如何调整以容纳顺式或反式脯氨酸。基于先前的观察结果，有人提出多个构象异构体只能容纳在蛋白质结构的柔性区域中。相比之下，在TB6的主要形式中以反式存在而在次要形式中以顺式存在的P22位于该结构域的刚性区域，这通过主链动力学测量得到证实。总体而言，主要和次要构象异构体的结构相似。然而，由于脯氨酸构象的变化，这两种形式的二级结构拓扑不同。
