PDZ-like domains mediate binding specificity in the Clp/Hsp100 family of chaperones and protease regulatory subunits.
ClpX, a molecular chaperone and the regulatory subunit of the ClpXP protease, is shown to contain tandem modular domains that bind to the C-terminal sequences of target proteins in a manner that parallels functional specificity. Nuclear magnetic resonance studies show that these C-terminal sequences are displayed as disordered peptides on the surface of otherwise folded proteins. The ClpX substrate-binding domains are homologous to sequences in other Clp/Hsp100 proteins and are related more distantly to PDZ domains, which also mediate C-terminal specific protein-protein interactions. Conservation of these binding domains indicates that the mode of substrate recognition characterized here for ClpX will be a conserved feature among Clp/Hsp100 family members and a distinguishing characteristic between this chaperone family and the Hsp70 chaperones.
Levchenko
I
I
Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139, USA.
Smith
C K
CK
Walsh
N P
NP
Sauer
R T
RT
Baker
T A
TA
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D049071:Endopeptidase Clp; D004926:Escherichia coli; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D015800:Protozoan Proteins / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism*
D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D015800:Protozoan Proteins; D012697:Serine Endopeptidases; D049071:Endopeptidase Clp; D000251:Adenosine Triphosphatases; C095049:ClpB protein, Leishmania; C088072:ClpX protein, E coli; D000074183:ATPases Associated with Diverse Cellular Activities