Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
J Biol Chem. 2011 Jul 1;286(26):22905-12. doi: 10.1074/jbc.M110.199984. Epub 2011 Apr 10.
The amino acid sequence of collagen is composed of GlyXaaYaa repeats. A prevailing paradigm maintains that stable collagen triple helices form when (2S)-proline (Pro) or Pro derivatives that prefer the C(γ)-endo ring pucker are in the Xaa position and Pro derivatives that prefer the C(γ)-exo ring pucker are in the Yaa position. Anomalously, an amino acid sequence in an invertebrate collagen has (2S,4R)-4-hydroxyproline (Hyp), a C(γ)-exo-puckered Pro derivative, in the Xaa position. In certain contexts, triple helices with Hyp in the Xaa position are now known to be hyperstable. Most intriguingly, the sequence (GlyHypHyp)(n) forms a more stable triple helix than does the sequence (GlyProHyp)(n). Competing theories exist for the physicochemical basis of the hyperstability of (GlyHypHyp)(n) triple helices. By synthesizing and analyzing triple helices with different C(γ)-exo-puckered proline derivatives in the Xaa and Yaa positions, we conclude that interstrand dipole-dipole interactions are the primary determinant of their additional stability. These findings provide a new framework for understanding collagen stability.
胶原蛋白的氨基酸序列由 GlyXaaYaa 重复组成。一个流行的范式认为，当（2S）-脯氨酸（Pro）或优先采用 C(γ)-内式环构象的 Pro 衍生物处于 Xaa 位置，而优先采用 C(γ)-外式环构象的 Pro 衍生物处于 Yaa 位置时，稳定的胶原蛋白三螺旋就会形成。异常的是，在一种无脊椎动物胶原蛋白中，一个氨基酸序列中的 Xaa 位置存在（2S,4R）-4-羟脯氨酸（Hyp），这是一种 C(γ)-外式环构象的 Pro 衍生物。在某些情况下，Xaa 位置存在 Hyp 的三螺旋现在被认为是超稳定的。最有趣的是，（GlyHypHyp)(n) 序列形成的三螺旋比（GlyProHyp)(n) 序列更稳定。对于（GlyHypHyp)(n) 三螺旋超稳定性的物理化学基础存在竞争理论。通过合成和分析 Xaa 和 Yaa 位置具有不同 C(γ)-外式环构象 Pro 衍生物的三螺旋，我们得出结论，链间偶极-偶极相互作用是其额外稳定性的主要决定因素。这些发现为理解胶原蛋白稳定性提供了一个新的框架。
