Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine.
The adaptor protein Hop mediates the association of the molecular chaperones Hsp70 and Hsp90. The TPR1 domain of Hop specifically recognizes the C-terminal heptapeptide of Hsp70 while the TPR2A domain binds the C-terminal pentapeptide of Hsp90. Both sequences end with the motif EEVD. The crystal structures of the TPR-peptide complexes show the peptides in an extended conformation, spanning a groove in the TPR domains. Peptide binding is mediated by electrostatic interactions with the EEVD motif, with the C-terminal aspartate acting as a two-carboxylate anchor, and by hydrophobic interactions with residues upstream of EEVD. The hydrophobic contacts with the peptide are critical for specificity. These results explain how TPR domains participate in the ordered assembly of Hsp70-Hsp90 multichaperone complexes.
Scheufler
C
C
Max-Planck Institute for Biochemistry, Martinsried, Germany.
Brinker
A
A
Bourenkov
G
G
Pegoraro
S
S
Moroder
L
L
Bartunik
H
H
Hartl
F U
FU
Moarefi
I
I
D001665:Binding Sites / Q000502:physiology; D003001:Cloning, Molecular; D017124:Conserved Sequence; D003461:Crystallography; D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D053612:Janus Kinases; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics; D014157:Transcription Factors; D014867:Water / Q000737:chemistry
D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D010446:Peptide Fragments; D014157:Transcription Factors; D014867:Water; D011505:Protein-Tyrosine Kinases; D053612:Janus Kinases; C085845:hop protein, Drosophila