Université Paris Cité and Université de la Réunion and Université des Antilles, INSERM, BIGR, DSIMB, F-75015 Paris, France.
Université Paris Cité and Université de la Réunion and Université des Antilles, INSERM, BIGR, DSIMB, F-97715 Saint Denis Messag, France.
Molecules. 2024 Oct 14;29(20):4863. doi: 10.3390/molecules29204863.
Camelids produce a special type of antibody, known as VHs, that has lost the V domain, providing a more optimised V domain. This particular highly stable antibody domain has interesting properties for biotechnological development. Ordinarily, those molecules possess only one disulphide bridge, but surprisingly, at least a quarter of these VHs have a second one. Curiously, this does not seem to be essential for the stability and the function of this domain. In an attempt to characterise precisely the role and impact of this disulphide bridge at the molecular level, several in silico mutants of a VH were created to disrupt this second disulphide bridge and those systems were submitted to molecular dynamics simulation. The loss of the second disulphide bridge leads to an increase in the flexibility of CDR1 and CDR3 and an unexpected rigidification of CDR2. Local conformational analysis shows local differences in the observed protein conformations. However, in fact, there is no exploration of new conformations but a change in the equilibrium between the different observed conformations. This explains why the interaction of VHs is not really affected by the presence or absence of this second bridge, but their rigidity is slightly reduced. Therefore, the additional disulphide bridge does not seem to be an essential part of VHs function.
骆驼科动物产生一种特殊类型的抗体，称为 VH，它失去了 V 结构域，提供了更优化的 V 结构域。这个特别稳定的抗体结构域具有有趣的生物技术开发特性。通常，这些分子只具有一个二硫键，但令人惊讶的是，至少四分之一的 VH 具有第二个二硫键。奇怪的是，这似乎对该结构域的稳定性和功能不是必需的。为了精确地描述该二硫键在分子水平上的作用和影响，创建了几个 VH 的计算机模拟突变体以破坏第二个二硫键，并将这些系统提交给分子动力学模拟。失去第二个二硫键会导致 CDR1 和 CDR3 的灵活性增加，而 CDR2 的刚性出乎意料地增加。局部构象分析显示观察到的蛋白质构象存在局部差异。然而，实际上，并没有探索新的构象，而是观察到的不同构象之间的平衡发生了变化。这解释了为什么 VH 的相互作用不受第二个桥的存在与否的影响，但其刚性略有降低。因此，额外的二硫键似乎不是 VH 功能的必要部分。
