Department of Physiology and Pharmacology, Texas A&M University, TVMC, College Station, TX 77843-4466, United States.
FEBS Lett. 2013 Nov 29;587(23):3787-91. doi: 10.1016/j.febslet.2013.09.043. Epub 2013 Oct 15.
Hepatocyte nuclear factor 4α (HNF4α) regulates liver type fatty acid binding protein (L-FABP) gene expression. Conversely as shown herein, L-FABP structurally and functionally also interacts with HNF4α. Fluorescence resonance energy transfer (FRET) between Cy3-HNF4α (donor) and Cy5-L-FABP (acceptor) as well as FRET microscopy detected L-FABP in close proximity (~80 Å) to HNF4α, binding with high affinity Kd ~250-300 nM. Circular dichroism (CD) determined that the HNF4α/L-FABP interaction altered protein secondary structure. Finally, L-FABP potentiated transactivation of HNF4α in COS7 cells. Taken together, these data suggest that L-FABP provides a signaling path to HNF4α activation in the nucleus.
肝细胞核因子 4α(HNF4α)调节肝型脂肪酸结合蛋白(L-FABP)基因的表达。相反,正如本文所示,L-FABP 在结构和功能上也与 HNF4α相互作用。Cy3-HNF4α(供体)和 Cy5-L-FABP(受体)之间的荧光共振能量转移(FRET)以及 FRET 显微镜检测到 L-FABP 与 HNF4α 接近(80 Å),结合具有高亲和力 Kd250-300 nM。圆二色性(CD)确定 HNF4α/L-FABP 相互作用改变了蛋白质二级结构。最后,L-FABP 增强了 COS7 细胞中 HNF4α 的转录激活。总之,这些数据表明 L-FABP 为 HNF4α 在核内的激活提供了信号通路。