Abstract：
:Molecular chaperones assist protein folding by facilitating their "forward" folding and preventing aggregation. However, once aggregates have formed, these chaperones cannot facilitate protein disaggregation. Bacterial ClpB and its eukaryotic homolog Hsp104 are essential proteins of the heat-shock response, which have the remarkable capacity to rescue stress-damaged proteins from an aggregated state. We have determined the structure of Thermus thermophilus ClpB (TClpB) using a combination of X-ray crystallography and cryo-electron microscopy (cryo-EM). Our single-particle reconstruction shows that TClpB forms a two-tiered hexameric ring. The ClpB/Hsp104-linker consists of an 85 A long and mobile coiled coil that is located on the outside of the hexamer. Our mutagenesis and biochemical data show that both the relative position and motion of this coiled coil are critical for chaperone function. Taken together, we propose a mechanism by which an ATP-driven conformational change is coupled to a large coiled-coil motion, which is indispensable for protein disaggregation.
journal_name
Celljournal_title
Cellauthors
Lee S,Sowa ME,Watanabe YH,Sigler PB,Chiu W,Yoshida M,Tsai FTdoi
10.1016/s0092-8674(03)00807-9subject
Has Abstractpub_date
2003-10-17 00:00:00pages
229-40issue
2eissn
0092-8674issn
1097-4172pii
S0092867403008079journal_volume
115pub_type
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