CHARACTERIZATION OF COLLAGEN-LIKE PEPTIDES CONTAINING INTERRUPTIONS IN THE REPEATING GLY-X-Y SEQUENCE
CHARACTERIZATION OF COLLAGEN-LIKE PEPTIDES CONTAINING INTERRUPTIONS IN THE REPEATING GLY-X-Y SEQUENCE
复制标题
DOI：
10.1021/bi00094a027
复制
发表时间：
1993-11-02
期刊：
影响因子：
2.9
通讯作者：
BRODSKY, B
中科院分区：
文献类型：
--
作者：
LONG, CG;BRASWELL, E;BRODSKY, B
在纤维状胶原蛋白中，沿着三螺旋的整个长度，每隔沿着一个残基就发现甘氨酸，但非纤维状胶原蛋白和其他蛋白质的三螺旋区域通常在这种重复模式中含有一个或多个中断。设计了一组四种肽来模拟（Gly-X-Y）n重复模式中的中断对三螺旋形成、稳定性和折叠的影响。在稳定的三螺旋肽（Pro-Hyp-Gly）10的中间，引入代表四种可能类别之一的中断：甘氨酸缺失、羟脯氨酸（Y位置）缺失、丙氨酸插入或甘氨酸至丙氨酸取代。如沉降平衡、NMR和CD研究所示，引入中断仍然允许在溶液中形成三聚体，但稳定性显著降低。失稳的程度和失稳的热力学基础取决于中断的类型。甘氨酸取代和丙氨酸插入的破坏性最小，其次是羟脯氨酸缺失，甘氨酸缺失是最不稳定的。我们的研究结果表明，在这些肽的断裂影响三螺旋构象和单体构象。这些研究为考虑胶原蛋白中不同类型中断的结构和功能后果提供了基础。
Glycine is found as every third residue along the entire length of triple helices in fibrillar collagens, but the triple-helix regions of nonfibrillar collagens and other proteins usually contain one or more interruptions in this repeating pattern. A set of four peptides was designed to model the effect of interruptions in the (Gly-X-Y)n repeating pattern on triple-helix formation, stability, and folding. Into the middle of the stable triple-helical peptide (Pro-Hyp-Gly)10, an interruption was introduced representing one of the four possible categories: a glycine deletion, a deletion of a hydroxyproline (Y position), an alanine insertion, or a glycine to alanine substitution. As shown by sedimentation equilibrium, NMR, and CD studies, the introduction of an interruption still allowed formation of trimers in solution, but with a marked decrease in stability. The degree of destabilization and the thermodynamic basis for the loss of stability depended on the type of interruption. The glycine substitution and alanine insertion were the least disruptive, followed by the hydroxyproline deletion, with the glycine deletion being the most destabilizing. Our results suggest that the breaks in these peptides affect both the triple-helical conformation and the monomer conformation. These studies provide a basis for considering the structural and functional consequences of different kinds of interruptions in collagen.