The M-Domain Controls Hsp104 Protein Remodeling Activity in an Hsp70/Hsp40-Dependent Manner

JOURNAL OF MOLECULAR BIOLOGY

卷:402

Article

Tsai, Francis T. F.¹ 

[1] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA

关键词: molecular chaperone;    AAA(+) machine;    protein disaggregase;    Hsp104;    ClpB;   

DOI  :  10.1016/j.jmb.2010.07.030

来源: Elsevier

【 摘 要 】

Yeast Hsp104 is a ring-forming ATP-dependent protein disaggregase that, together with the cognate Hsp70 chaperone system, has the remarkable ability to rescue stress-damaged proteins from a previously aggregated state. Both upstream and downstream functions for the Hsp70 system have been reported, but it remains unclear how Hsp70/Hsp40 is coupled to Hsp104 protein remodeling activity. Hsp104 is a multidomain protein that possesses an N-terminal domain, an M-domain, and two tandem AAA(+) domains. The M-domain forms an 85-angstrom long coiled coil and is a hallmark of the Hsp104 chaperone family. While the three-dimensional structure of Hsp104 has been determined, the function of the M-domain is unclear. Here, we demonstrate that the M-domain is essential for protein disaggregation, but dispensable for Hsp104 ATPase- and substrate-translocating activities. Remarkably, replacing the Hsp104 M-domain with that of bacterial ClpB, and vice versa, switches species specificity so that our chimeras now cooperate with the noncognate Hsp70/DnaK chaperone system. Our results demonstrate that the M-domain controls Hsp104 protein remodeling activities in an Hsp70/Hsp40-dependent manner, which is required to unleash Hsp104 protein disaggregating activity. (C) 2010 Elsevier Ltd. All rights reserved.

【 授权许可】

Free