Kozak John J, Gray Harry B, Garza-López Roberto A
DePaul University , 243 South Wabash Avenue, Chicago, Illinois 60604-6116, United States.
Beckman Institute, California Institute of Technology , Pasadena, California 91125, United States.
J Phys Chem B. 2016 Nov 23;120(46):11888-11896. doi: 10.1021/acs.jpcb.6b08691. Epub 2016 Nov 11.
We study the structural stability of helical and nonhelical regions in chain A of human intelectin-1. Using a geometrical model introduced previously, we carried out a computational analysis based on the recently reported crystal structure of this protein by Kiessling et al. to quantify the resiliency of the native state to steric perturbations. Response to these perturbations is characterized by calculating, relative to the native state, the lateral, radial, and angular displacements of n-residue segments of the polypeptide chain centered on each residue. By quantifying the stability of the protein through six stages of unfolding, we are able to identify regions in chain A of intelectin-1 that are markedly affected by structural perturbations versus those that are relatively unaffected, the latter suggesting that the native-state geometry of these regions is essentially conserved. Importantly, residues in the vicinity of calcium ions comprise a conserved region, suggesting that Ca ions play a role not only in the coordination of carbohydrate hydroxyl groups but also in preserving the integrity of the structure.
我们研究了人 intelectin-1 的 A 链中螺旋和非螺旋区域的结构稳定性。使用先前引入的几何模型，我们基于 Kiessling 等人最近报道的该蛋白质的晶体结构进行了计算分析，以量化天然状态对空间位阻扰动的弹性。相对于天然状态，通过计算以每个残基为中心的多肽链 n 残基片段的横向、径向和角向位移来表征对这些扰动的响应。通过量化蛋白质在六个展开阶段的稳定性，我们能够确定 intelectin-1 的 A 链中受结构扰动显著影响的区域与相对不受影响的区域，后者表明这些区域的天然状态几何结构基本保守。重要的是，钙离子附近的残基构成一个保守区域，这表明钙离子不仅在碳水化合物羟基的配位中起作用，而且在保持结构的完整性方面也起作用。
