Brodsky Barbara, Thiagarajan Geetha, Madhan Balaraman, Kar Karunakar
Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Biopolymers. 2008 May;89(5):345-53. doi: 10.1002/bip.20958.
Peptides have been an integral part of the collagen triple-helix structure story, and have continued to serve as useful models for biophysical studies and for establishing biologically important sequence-structure-function relationships. High resolution structures of triple-helical peptides have confirmed the basic Ramachandran triple-helix model and provided new insights into the hydration, hydrogen bonding, and sequence dependent helical parameters in collagen. The dependence of collagen triple-helix stability on the residues in its (Gly-X-Y)(n) repeating sequence has been investigated by measuring melting temperatures of host-guest peptides and an on-line collagen stability calculator is now available. Although the presence of Gly as every third residue is essential for an undistorted structure, interruptions in the repeating (Gly-X-Y)(n) amino acid sequence pattern are found in the triple-helical domains of all nonfibrillar collagens, and are likely to play a role in collagen binding and degradation. Peptide models indicate that small interruptions can be incorporated into a rod-like triple-helix with a highly localized effect, which perturbs hydrogen bonds and places the standard triple-helices on both ends out of register. In contrast to natural interruptions, missense mutations which replace one Gly in a triple-helix domain by a larger residue have pathological consequences, and studies on peptides containing such Gly substitutions clarify their effect on conformation, stability, and folding. Recent studies suggest peptides may also be useful in defining the basic principles of collagen self-association to the supramolecular structures found in tissues.
肽一直是胶原蛋白三螺旋结构研究的重要组成部分，并持续作为生物物理研究以及建立生物学上重要的序列 - 结构 - 功能关系的有用模型。三螺旋肽的高分辨率结构证实了基本的拉马钱德兰三螺旋模型，并为胶原蛋白中的水合作用、氢键以及序列依赖性螺旋参数提供了新的见解。通过测量主 - 客体肽的解链温度，研究了胶原蛋白三螺旋稳定性对其（Gly - X - Y）（n）重复序列中残基的依赖性，并且现在有一个在线胶原蛋白稳定性计算器可用。虽然每隔三个残基存在甘氨酸对于未扭曲的结构至关重要，但在所有非纤维状胶原蛋白的三螺旋结构域中都发现了重复的（Gly - X - Y）（n）氨基酸序列模式的中断，并且这些中断可能在胶原蛋白的结合和降解中起作用。肽模型表明，小的中断可以以高度局部化的效应并入棒状三螺旋中，这会扰乱氢键并使两端的标准三螺旋错位。与天然中断相反，在三螺旋结构域中用较大残基取代一个甘氨酸的错义突变具有病理后果，对含有此类甘氨酸取代的肽的研究阐明了它们对构象、稳定性和折叠的影响。最近的研究表明，肽在定义胶原蛋白自组装成组织中发现的超分子结构的基本原理方面也可能有用。
