Fernández Ariel
Indiana University School of Informatics and Center for Computational Biology and Bioinformatics, Indiana University Medical School, 714 N. Senate Avenue Suite 250, Indianapolis, IN 46202, USA.
J Mol Biol. 2004 Mar 19;337(2):477-83. doi: 10.1016/j.jmb.2004.01.050.
Soluble proteins preserve their structure only if a sufficient number of non-polar groups are clustered around the backbone hydrogen bonds, protecting them from water attack. When these bonds are not properly wrapped or dehydrated intramolecularly, structural integrity can be preserved through binding partnerships. This is because insufficiently wrapped hydrogen bonds are inherently adhesive and become better shielded upon protein-ligand association. Thus, we postulate that deficiently wrapped hydrogen bonds are functionally relevant. Two findings that support this conjecture are: (a) there is a statistically relevant linear correlation between the number of defects in a folding domain and its proteomic connectivity, obtained from large-scale two-hybrid experiments; (b) the residues paired by under-wrapped hydrogen bonds are highly conserved. The high mutational sensitivity of under-wrapped regions can be rationalized, since their structural integrity relies on their propensity to behave as binding sites, in turn, a consequence of their adhesiveness. Thus, the regions in soluble protein structure that cannot be kept dry in water tend to be conserved.
可溶性蛋白质只有在足够数量的非极性基团聚集在主链氢键周围，保护它们免受水的攻击时，才能保持其结构。当这些键在分子内没有被妥善包裹或脱水时，可以通过结合伙伴关系来保持结构完整性。这是因为包裹不充分的氢键本质上具有粘性，在蛋白质-配体结合时会得到更好的屏蔽。因此，我们推测包裹不足的氢键具有功能相关性。支持这一推测的两个发现是：（a）在折叠结构域中的缺陷数量与其蛋白质组连接性之间存在统计学上相关的线性相关性，这是通过大规模双杂交实验获得的；（b）由包裹不足的氢键配对的残基高度保守。包裹不足区域的高突变敏感性是可以解释的，因为它们的结构完整性依赖于它们作为结合位点的倾向，而这又是它们粘性的结果。因此，可溶性蛋白质结构中在水中无法保持干燥的区域往往是保守的。
