Sharp Adam, Cutress Ramsey I, Johnson Peter W M, Packham Graham, Townsend Paul A
Cancer Research UK Centre, Cancer Sciences Division, University of Southampton, School of Medicine, Southampton General Hospital, Southampton S016 6YD, UK.
FEBS Lett. 2009 Nov 3;583(21):3405-11. doi: 10.1016/j.febslet.2009.09.047. Epub 2009 Oct 1.
BAG-1, a multifunctional protein, interacts with a plethora of cellular targets where the interaction with HSC70 and HSP70, is considered vital. Structural studies have demonstrated the C-terminal of BAG-1 forms a bundle of three alpha-helices of which helices 2 and 3 are directly involved in binding to the chaperones. Here we found peptides derived from helices 2 and 3 of BAG-1 interfered with BAG-1:HSC70 binding. We confirmed that a 12 amino-acid peptide from helix 2 directly interacted with HSC70 and when introduced into MCF-7 and ZR-75-1 cells, these peptides inhibited their growth. In conclusion, we have identified a small domain within BAG-1 which appears to play a critical role in the interaction with HSC70.
BAG-1是一种多功能蛋白质，它与大量细胞靶点相互作用，其中与热休克蛋白70（HSC70）和热休克蛋白70（HSP70）的相互作用被认为至关重要。结构研究表明，BAG-1的C末端形成一束由三个α螺旋组成的结构，其中螺旋2和螺旋3直接参与与伴侣蛋白的结合。在这里，我们发现源自BAG-1螺旋2和螺旋3的肽干扰了BAG-1与HSC70的结合。我们证实，来自螺旋2的一个12氨基酸肽直接与HSC70相互作用，当将这些肽引入MCF-7和ZR-75-1细胞时，它们会抑制细胞生长。总之，我们在BAG-1中鉴定出一个小结构域，该结构域似乎在与HSC70的相互作用中起关键作用。
