The triple helical structure and stability of collagen model peptide with 4(s)-hydroxyprolyl-pro-gly units
The triple helical structure and stability of collagen model peptide with 4(s)-hydroxyprolyl-pro-gly units
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DOI：
10.1002/bip.21730
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发表时间：
2012-01-01
期刊：
影响因子：
2.9
通讯作者：
Kobayashi, Yuji
中科院分区：
文献类型：
--
作者：
Motooka, Daisuke;Kawahara, Kazuki;Kobayashi, Yuji
对胶原蛋白结构的广泛研究表明，具有典型（X-Y-Gly）n重复序列（X和Y：Pro及其类似物）的多种模型肽中Pro残基的羟基化是影响三螺旋稳定性的主要因素之一。虽然 Y 位上的 (2S,4R)-羟脯氨酸 (Hyp) 稳定了三螺旋，但 X 位上的 (2S,4S)-羟脯氨酸 (hyp) 使螺旋不稳定，这表明 (hyp-Pro-Gly)15 的三螺旋不如 (Pro-Pro-Gly)15 稳定，并且较短的肽 (hyp-Pro-Gly)10 不会形成三螺旋 螺旋。为了阐明Pro残基的羟基在胶原三螺旋稳定机制中的作用，我们合成并结晶了模型肽(Pro-Hyp-Gly)4-(hyp-Pro-Gly)2-(Pro-Hyp-Gly)4，并通过X射线晶体学和CD光谱分析了其结构。在晶体中，该肽的主链形成典型的胶原蛋白状三螺旋。大多数hyp残基以极浅的角度折叠褶皱，可能是为了减轻空间位阻，但其余残基将羟基基团向溶剂突出，具有不太有利的向上褶皱以适应三螺旋。没有迹象表明 hyp 的羟基部分和羰基氧之间存在分子内氢键，而 hyp 被认为会破坏三螺旋的稳定性。我们还通过量子力学计算比较了 Ac-hyp-NMe2 中吡咯烷环上下封隔器的构象能。 (C) 2011 Wiley periodicals, Inc. 生物聚合物（Pept Sci）98：111121，2012。
Extensive studies on the structure of collagen have revealed that the hydroxylation of Pro residues in a variety of model peptides with the typical (X-Y-Gly)nrepeats (X and Y: Pro and its analogues) represents one of the major factors influencing the stability of triple helices. While(2S,4R)-hydroxyproline (Hyp) at the position Y stabilizes the triple helix, (2S,4S)-hydroxyproline (hyp) at the X-position destabilizes the helix as demonstrated that the triple helix of (hyp-Pro-Gly)15 is less stable than that of (Pro-Pro-Gly)15 and that a shorter peptide (hyp-Pro-Gly)10 does not form the helix. To clarify the role of the hydroxyl group of Pro residues to play in the stabilization mechanism of the collagen triple helix, we synthesized and crystallized a model peptide (Pro-Hyp-Gly)4-(hyp-Pro-Gly)2-(Pro-Hyp-Gly)4 and analyzed its structure by X-ray crystallography and CD spectroscopy. In the crystal, the main-chain of this peptide forms a typical collagen like triple helix. The majority of hyp residues take down pucker with exceptionally shallow angles probably to relieve steric hindrance, but the remainders protrude the hydroxyl group toward solvent with the less favorable up pucker to fit in a triple helix. There is no indication of the existence of an intra-molecular hydrogen bond between the hydroxyl moiety and the carbonyl oxygen of hyp supposed to destabilize the triple helix. We also compared the conformational energies of up and down packers of the pyrrolidine ring in Ac-hyp-NMe2 by quantum mechanical calculations. (C) 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 98: 111121, 2012.