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Three‐dimensional Structure of a Prion‐remodeling Machine
Author(s) -
Tsai Francis T.,
Sielaff Bernhard,
Lee Sukyeong
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.672.3
Subject(s) - clpb , random hexamer , yeast , biology , protein structure , chaperone (clinical) , biochemistry , computational biology , chemistry , microbiology and biotechnology , biophysics , heat shock protein , gene , medicine , pathology
Bacterial ClpB and its yeast ortholog Hsp104 are ATP‐dependent molecular machines, which have the remarkable ability to rescue proteins from a previously aggregated state. In addition to its role in thermotolerance, Hsp104 is also essential for the inheritance, maintenance and elimination of [PSI+], a yeast prion that increases translational read‐through of nonsense codons. The prion‐remodeling activity is unique to Hsp104 and, unlike its protein disaggregating function, is not shared with ClpB. The cryo‐EM structure of Hsp104 was determined recently and was used to generate a 3D model of the Hsp104 hexamer (Wendler et al. , CELL 2007). Surprisingly, the proposed Hsp104 model differed dramatically from the 3D structure of ClpB (Lee et al. , CELL 2003; MOL. CELL 2007). This of course has significant mechanistic implications, including substrate interaction and the disaggregation of previously aggregated proteins. To address this question we set‐out to determine the 3D structure of Hsp104 using innovative, multi‐pronged structural and biochemical approaches. Our new results suggest that ClpB and Hsp104 are more similar in structure than previously proposed. The mechanistic implication of our new structural insight will be discussed at this meeting.