Tuning of chaperone activity of Hsp70 proteins by modulation of nucleotide exchange.
The Hsp70 chaperone activity in protein folding is regulated by ATP-controlled cycles of substrate binding and release. Nucleotide exchange plays a key role in these cycles by triggering substrate release. Structural searches of Hsp70 homologs revealed three structural elements within the ATPase domain: two salt bridges and an exposed loop. Mutational analysis showed that these elements control the dissociation of nucleotides, the interaction with exchange factors and chaperone activity. Sequence variations in the three elements classify the Hsp70 family members into three subfamilies, DnaK proteins, HscA proteins and Hsc70 proteins. These subfamilies show strong differences in nucleotide dissociation and interaction with the exchange factors GrpE and Bag-1.
Brehmer
D
D
Institut für Biochemie und Molekularbiologie, Albert-Ludwigs-Universität Freiburg, Hermann-Herder-Str. 7, D-79104 Freiburg, Germany.
Rüdiger
S
S
Gässler
C S
CS
Klostermeier
D
D
Packschies
L
L
Reinstein
J
J
Mayer
M P
MP
Bukau
B
B
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D055672:Static Electricity; D013379:Substrate Specificity; D014157:Transcription Factors
C091732:BCL2-associated athanogene 1 protein; D001426:Bacterial Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C068113:GrpE protein, Bacteria; C489400:GrpE protein, E coli; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D006360:Heat-Shock Proteins; D014157:Transcription Factors; C085650:hscA protein, E coli; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C063842:dnaK protein, E coli