Takayama S, Xie Z, Reed J C
The Burnham Institute, La Jolla, California 92037, USA.
J Biol Chem. 1999 Jan 8;274(2):781-6. doi: 10.1074/jbc.274.2.781.
Heat Shock Protein 70 kDa (Hsp70) family molecular chaperones play critical roles in protein folding and trafficking in all eukaryotic cells. The mechanisms by which Hsp70 family chaperones are regulated, however, are only partly understood. BAG-1 binds the ATPase domains of Hsp70 and Hsc70, modulating their chaperone activity and functioning as a competitive antagonist of the co-chaperone Hip. We describe the identification of a family of BAG-1-related proteins from humans (BAG-2, BAG-3, BAG-4, BAG-5), the invertebrate Caenorhabditis elegans (BAG-1, BAG-2), and the fission yeast Schizosaccharomyces pombe (BAG-1A, BAG-1B). These proteins all contain a conserved approximately 45-amino acid region near their C termini (the BAG domain) that binds Hsc70/Hsp70, but they differ widely in their N-terminal domains. The human BAG-1, BAG-2, and BAG-3 proteins bind with high affinity (KD congruent with 1-10 nM) to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner. The findings suggest opportunities for specification and diversification of Hsp70/Hsc70 chaperone functions through interactions with various BAG-family proteins.
70kDa热休克蛋白（Hsp70）家族分子伴侣在所有真核细胞的蛋白质折叠和运输过程中发挥着关键作用。然而，Hsp70家族伴侣蛋白的调控机制仅得到部分了解。BAG-1与Hsp70和Hsc70的ATP酶结构域结合，调节它们的伴侣活性，并作为共伴侣蛋白Hip的竞争性拮抗剂发挥作用。我们描述了从人类（BAG-2、BAG-3、BAG-4、BAG-5）、无脊椎动物秀丽隐杆线虫（BAG-1、BAG-2）和裂殖酵母粟酒裂殖酵母（BAG-1A、BAG-1B）中鉴定出的一类BAG-1相关蛋白。这些蛋白在其C末端附近（BAG结构域）都含有一个保守的约45个氨基酸的区域，该区域可与Hsc70/Hsp70结合，但它们的N末端结构域差异很大。人类BAG-1、BAG-2和BAG-3蛋白以高亲和力（KD约为1-10 nM）与Hsc70的ATP酶结构域结合，并以一种可被Hip抑制的方式抑制其伴侣活性。这些发现表明，通过与各种BAG家族蛋白相互作用，Hsp70/Hsc70伴侣功能具有特异性和多样化的机会。
