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Protein Unfolding by E. coli ClpB, an AAA+ Protein
Author(s) -
Miller Jonathan J.,
Doyle Shan M.,
Hoskins Joel R.,
Wickner Sue
Publication year - 2007
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.21.6.lb30-a
Subject(s) - clpb , protein aggregation , escherichia coli , proteostasis , biochemistry , chaperone (clinical) , biology , cyclic nucleotide binding domain , protein folding , nucleotide , thermus thermophilus , aaa proteins , chemistry , microbiology and biotechnology , biophysics , enzyme , gene , medicine , pathology , atpase
Life is dependent upon correctly folded and biologically active proteins. Protein misfolding and aggregation are associated with a variety of diseases such as Alzheimer’s disease, type II diabetes, and prion‐mediated infections. Escherichia coli ClpB and its yeast homolog, Hsp104, in conjunction with the DnaK/Hsp70 chaperone system, have been shown to dissolve and reactivate disaggregated proteins in vivo and in vitro . ClpB belongs to the ring forming Clp/Hsp100 protein class, part of the AAA+ superfamily of proteins. ClpB has two nucleotide binding domains (NBDs), which categorizes it as a class I AAA+ protein. Distinguishing it from its class I counterparts is ClpB’s long, coiled coil middle domain inserted within the NBD‐1 domain, a characteristic believed to be essential in its unique dissaggregase activities. In vitro , ClpB functions independently of the DnaK system in protein unfolding, remodeling and disaggregation when provided mixtures of ATP and ATPγS, a nonphysiological and poorly hydrolyzed ATP analog. We have tested other nucleotide combinations and various protein substrates to gain an understanding of how ClpB acts and how its action is regulated by nucleotide.