胰岛素超级家族蛋白质的累积系谱,序列和结构分析提供了独特的结构功能洞察力
Shrilakshmi Sheshagiri Rao1,2, Shankar V Kundapura1,2, Debayan Dey1,3
1Division of Biological Sciences, Poornaprajna Institute of Scientific Research, Poornaprajnapura, 562110, Bidalur (Post), Bengaluru, India.
Molecular informatics
|July 8, 2024
概括
胰岛素超级家族蛋白 (ISP) 显示高IGFs序列保存,表明对多样性的耐药性. 这项研究重新定义了放松素的动机,并为治疗开发提出了新的胰岛素裂变部位.
科学领域:
- 进化生物学是进化的生物学.
- 结构生物学是结构生物学.
- 生物化学 生物化学
背景情况:
- 胰岛素超级家族蛋白质 (ISP),包括胰岛素,IGF和放松素,是重要的生理调节器.
- 这些蛋白质是从一个共同的祖先进化而来的,尽管有功能上的分歧,但它们保留了由二硫化物键稳定的类似结构.
- 最近在序列和结构数据方面的进步需要对ISP进行全面的演变分析.
研究的目的:
- 分析427个ISP序列的演变,整合功能和结构数据.
- 研究IGF的高序列保存及其结构基础.
- 更新relaxin家族的受体结合签名图案,并探索胰岛素C裂变.
主要方法:
- 对427个ISP序列进行比较序列分析.
- 基于结构的分析,以合理化序列保存.
- 分子动力学模拟以支持拟议的机制和治疗应用.
主要成果:
- 在184个序列中,IGFs表现出异常高的序列保存率 (>90%),提出基于结构的解释.
- 提供了对各种放松素家族成员的受体结合特征图案的更新定义.
- 在某些胰岛素序列中确定了可能的非正规的C-裂部位.
结论:
- 高IGFs的保存归因于生理关键相互作用的强有力的选择性压力.
- 在特定的胰岛素变体中提出了C-裂的机制.
- 重新定义的放松因子和对ISP演变的洞察力为开发具有治疗潜力的向胰岛素突变物提供了基础.
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