Eisenman Helene C, Craig Elizabeth A
Program in Cellular and Molecular Biology, and Department of Biochemistry, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, USA.
Mol Microbiol. 2004 Jul;53(1):335-44. doi: 10.1111/j.1365-2958.2004.04134.x.
Ssz1 (Pdr13) and Zuo1, members of the Hsp70 and J-protein molecular chaperone families, respectively, form a heterodimer and function on the ribosome with the Hsp70, Ssb, presumably assisting folding of newly synthesized polypeptides. As it has also been reported that Ssz1 induces pleiotropic drug resistance (PDR) when overexpressed, a possible role for Zuo1 in PDR was investigated. The C-terminal domain of Zuo1, which is dispensable for Zuo1's chaperone function on the ribosome, is both necessary and sufficient for PDR induction by Zuo1. A single domain of Ssz1, the N-terminal ATPase domain, is sufficient for PDR induction as well, indicating that Ssz1 does not function as a chaperone in PDR. No role for Ssb was found in PDR; overexpression did not affect PDR, nor was its presence required for Ssz1's or Zuo1's effect on PDR. As our results also indicate that Ssz1 and Zuo1 must be free of ribosomes to induce PDR, we propose that Ssz1's and Zuo1's function in PDR is distinct from their role as ribosome-associated co-chaperones and may be regulatory in nature.
Ssz1（Pdr13）和Zuo1分别是Hsp70和J蛋白分子伴侣家族的成员，它们形成异二聚体，并与Hsp70、Ssb在核糖体上发挥作用，大概是协助新合成多肽的折叠。由于也有报道称Ssz1过表达时会诱导多药耐药性（PDR），因此研究了Zuo1在PDR中的可能作用。Zuo1的C末端结构域对于Zuo1在核糖体上的伴侣功能是可有可无的，但对于Zuo1诱导PDR来说既是必要的也是充分的。Ssz1的单个结构域，即N末端ATP酶结构域，也足以诱导PDR，这表明Ssz1在PDR中并不作为伴侣发挥作用。未发现Ssb在PDR中有作用；过表达不影响PDR，Ssz1或Zuo1对PDR的作用也不需要它的存在。由于我们的结果还表明Ssz1和Zuo1必须脱离核糖体才能诱导PDR，我们提出Ssz1和Zuo1在PDR中的功能与其作为核糖体相关共伴侣的作用不同，可能本质上是调节性的。
