温度诱导的整合素 αvβ3 受体结构变化及其与 RGD 肽配体的相互作用,Peptide Science

当前位置： X-MOL 学术 › Pept. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

温度诱导的整合素 αvβ3 受体结构变化及其与 RGD 肽配体的相互作用
Peptide Science ( IF 1.5 ) Pub Date : 2022-12-28 , DOI: 10.1002/pep2.24302
Anqi Wang _{1,

2} , Kai Yue _{1,

2} , Yiang Wei ₁ , Weishen Zhong _{1,

2} , Genpei Zhang _{1,

2}

Affiliation

受体蛋白在高温下的结构变化是影响热疗和药物递送联合治疗的配体安装纳米载体靶向能力的因素之一。本研究从理论和实验两方面研究了整合素 αvβ3 受体与精氨酸-甘氨酸-天冬氨酸 (RGD) 肽配体在高温下的结合行为和机制。通过分子动力学模拟计算不同温度下整合素αvβ3的结构参数以及RGD肽与整合素αvβ3在不同结合位点的相互作用力。傅里叶变换红外光谱、能量色散光谱、紫外-可见吸收光谱、和原子力显微镜用于分析整合素 αvβ3 的结构变化并测量配体-受体相互作用。结果表明，随着温度的升高，整合素αvβ3的氢键数量减少，二级结构发生变化，表明整合素αvβ3发生了变性。整合素αv亚基在高温下的结构稳定性优于整合素β3亚基。随着温度升高，RGD 肽与整合素 αvβ3 之间的相互作用减弱，因为整合素 αvβ3 结合位点的结构变得更加灵活，并且相应的钙离子从结合位点脱落。

"点击查看英文标题和摘要"

Temperature-induced structural change of integrin αvβ3 receptor and its interaction with the RGD peptide ligand

The structural change of receptor protein at high temperatures is one of the factors affecting the targeting ability of ligand-installed nanocarriers for combined therapy of hyperthermia and drug delivery. In this study, the binding behaviors and mechanisms of integrin αvβ3 receptor and the arginine-glycine-aspartic acid (RGD) peptide ligand at high temperatures were investigated both theoretically and experimentally. The structural parameters of integrin αvβ3 at different temperatures and the interaction forces between the RGD peptide and integrin αvβ3 at different binding sites were calculated by molecular dynamics simulation. Fourier transform infrared spectroscopy, energy dispersive spectroscopy, ultraviolet–visible absorption spectroscopy, and atomic force microscopy were used to analyze the structural changes of integrin αvβ3 and to measure the ligand-receptor interaction. Results show that the number of hydrogen bonds decreased and the secondary structure of integrin αvβ3 changed with the increase in temperature, indicating the denaturation of integrin αvβ3. The structural stability of the integrin αv subunit was better than that of the integrin β3 subunit at high temperatures. The interaction between the RGD peptide and integrin αvβ3 weakened as the temperature increased because the structure of the integrin αvβ3 binding site became more flexible and the corresponding calcium ions were shed from the binding site. The strongest interaction force was exhibited at the binding site of the integrin β3 subunit at 310 K while it was found at the binding site of the integrin αv subunit at higher temperatures, owing to the smaller structure deformation of the integrin αv subunit.

更新日期：2022-12-28

点击分享查看原文

点击收藏

阅读更多本刊新发论文