López-Sánchez Rubén, Laurents Douglas V, Mompeán Miguel
Instituto de Química Física "Blas Cabrera" - CSIC, Madrid, Spain.
Commun Chem. 2024 Aug 30;7(1):191. doi: 10.1038/s42004-024-01268-2.
Hydrogen bond cooperativity (HBC) plays an important role in stabilizing protein assemblies built by α-helices and β-sheets, the most common secondary structures. However, whether HBC exists in other types of protein secondary structures such as polyproline II (PPII) helices remains unexplored. This is intriguing, since PPII systems as assembling blocks are continuously emerging across multiple fields. Here, using a combination of computational chemistry tools and molecular modeling corroborated by experimental observables, we characterize the distinct H-bonding patterns present in PPII helical bundles and establish that HBC stabilizes intermolecular PPII helices as seen in other protein assemblies such as amyloid fibrils. In addition to cooperative interactions in canonical CO···HN H-bonds, we show that analogous interactions in non-canonical CO···HC H-bonds are relevant in Gly-rich PPII bundles, thus compensating for the inability of glycine residues to create hydrophobic cores. Our results provide a mechanistic explanation for the assembly of these bundles.
氢键协同性（HBC）在稳定由α螺旋和β折叠（最常见的二级结构）构建的蛋白质聚集体中起着重要作用。然而，HBC是否存在于其他类型的蛋白质二级结构中，如多聚脯氨酸II（PPII）螺旋，仍未得到探索。这很有趣，因为作为组装单元的PPII系统在多个领域不断涌现。在这里，我们结合计算化学工具和分子建模，并通过实验观测结果进行佐证，表征了PPII螺旋束中存在的独特氢键模式，并确定HBC能够稳定分子间PPII螺旋，就像在淀粉样纤维等其他蛋白质聚集体中看到的那样。除了在典型的CO···HN氢键中的协同相互作用外，我们还表明，在富含甘氨酸的PPII束中，非典型的CO···HC氢键中的类似相互作用也很重要，从而弥补了甘氨酸残基无法形成疏水核心的不足。我们的结果为这些束的组装提供了一个机理解释。
