脂肪酸结合蛋白质结构的高分辨率数据集. I. FABP4和配体结合的动力学
Fabio Casagrande1, Andreas Ehler1, Dominique Burger1
1Therapeutic Modalities, Innovation Center Basel, F. Hoffmann-La Roche, Grenzacherstrasse 124, 4070 Basel, Switzerland.
Acta crystallographica. Section D, Structural biology
|August 1, 2025
概括
脂肪酸结合蛋白 (FABPs) 在结合联体时变硬,影响它们与膜的相互作用. 这种相互作用决定了FABP4是否进入细胞核,从而影响其生物作用.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 脂肪酸结合蛋白 (FABP) 促进脂肪酸的运输,促进新陈代谢和基因调节.
- 已知FABP与细胞膜相互作用,并且可以转移到细胞核中.
研究的目的:
- 研究脂肪酸和抑制剂如何影响人类FABP4 (hFABP4) 的结构灵活性和膜关联.
- 阐明联体结合影响hFABP4与膜的相互作用及其核导入潜力的机制.
主要方法:
- 使用了核磁共振 (NMR) 光谱学.
- 使用了没有内源性配体的人类FABP4 (hFABP4) 制剂.
- 研究涉及各种脂肪酸和抑制剂对hFABP4构造和双细胞/膜协会的影响.
主要成果:
- 包括脂肪酸和抑制剂在内的带结合会诱导hFABP4的刚性,特别是在门区.
- hFABP4与双细胞/膜的结合是依赖于连接体的,导致持续结合或分离到溶液中.
- 氨基酸残留物Phe58在确定基于联体体积的hFABP4分离方面发挥着至关重要的作用.
结论:
- 在hFABP4中依赖质的形状变化决定了它的膜关联和随后的细胞定位.
- 从膜中分离hFABP4是其非经典核进口通路的先决条件.
- 这种依赖于连接体的膜脱离和核进口激活的机制可能在其他FABP异构体中保持.
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