Premium
Characterization of the Effects of Lipid‐binding on the Chaperone Activities of 70‐kDa Heat‐Shock Proteins
Author(s) -
McCallister Chelsea Marie,
Nikolaidis Nikolas
Publication year - 2012
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.26.1_supplement.997.3
Subject(s) - chaperone (clinical) , heat shock protein , biochemistry , plasma protein binding , binding protein , intracellular , binding site , microbiology and biotechnology , chemistry , biology , biophysics , medicine , pathology , gene
Hsp70s are a group of molecular chaperones essential for cellular homeostasis and survival. Apart from their indispensable intracellular functions, Hsp70s are also found in close proximity to biological membranes and the extracellular environment, where they activate the immune system and function in cell signaling. It is also known that Hsp70s interact and bind to the primary constituent of membranes, the lipids. However, it is currently unknown whether lipid‐binding affects their chaperone functions. To determine the mechanistic role that lipid‐binding plays on the function of Hsp70s as molecular chaperones we tested the effects of lipid‐binding on the interaction of Hsp70s with nucleotides and protein substrates, as well as whether lipid‐binding affects their refolding abilities. Our results show that lipid‐binding is altered when HSPA1A binds to nucleotides, while it remains unaffected when the protein binds to protein substrates. Furthermore, we show that lipid‐binding significantly reduces the refolding activity of HSPA1A. Taking into account the fact that lipid‐binding is mediated by the nucleotide‐binding domain of the protein, we speculate that a specific conformational change caused by the lipid‐binding reduces the ATPase activity and subsequently the refolding activity of the chaperone. These data strongly suggest that lipid‐binding regulates the chaperone activities of Hsp70s. This project was supported by funds from CSUPERB and CSUF to NN.