Malcor Jean-Daniel, Ferruz Noelia, Romero-Romero Sergio, Dhingra Surbhi, Sagar Vamika, Jalan Abhishek A
Laboratory of Tissue Biology and Therapeutic Engineering, CNRS UMR 5305 University of Lyon, Lyon, France.
Department of Biochemistry, University of Bayreuth, Bayreuth, Germany.
Nat Commun. 2025 Mar 19;16(1):2702. doi: 10.1038/s41467-024-54046-y.
Collagen proteins contain a characteristic structural motif called a triple helix. During the self-assembly of this motif, three polypeptides form a folding nucleus at the C-termini and then propagate towards the N-termini like a zip-chain. While polypeptides from human collagens contain up to a 1000 amino acids, those found in bacteria can contain up to 6000 amino acids. Additionally, the collagen polypeptides are also frequently interrupted by non-helical sequences that disrupt folding and reduce stability. Given the length of polypeptides and the disruptive interruptions, compensating mechanisms that stabilize against local unfolding during propagation and offset the entropic cost of folding are not fully understood. Here, we show that the information for the correct folding of collagen triple helices is encoded in their sequence as interchain electrostatic interactions, which likely act as molecular clamps that prevent local unfolding. In the case of humans, disrupting these electrostatic interactions is associated with severe to lethal diseases.
胶原蛋白含有一种名为三螺旋的特征性结构基序。在该基序的自组装过程中，三条多肽在C端形成一个折叠核，然后像拉链一样向N端延伸。人类胶原蛋白的多肽含有多达1000个氨基酸，而细菌中的胶原蛋白多肽则可含有多达6000个氨基酸。此外，胶原蛋白多肽还经常被非螺旋序列打断，这些序列会破坏折叠并降低稳定性。鉴于多肽的长度和破坏性中断，在延伸过程中稳定局部解折叠并抵消折叠熵成本的补偿机制尚未完全了解。在这里，我们表明胶原蛋白三螺旋正确折叠的信息编码在其序列中，作为链间静电相互作用，这可能充当防止局部解折叠的分子钳。就人类而言，破坏这些静电相互作用与严重至致命的疾病有关。
