Chaperone ligand-discrimination by the TPR-domain protein Tah1.
Tah1 [TPR (tetratricopeptide repeat)-containing protein associated with Hsp (heat-shock protein) 90] has been identified as a TPR-domain protein. TPR-domain proteins are involved in protein-protein interactions and a number have been characterized that interact either with Hsp70 or Hsp90, but a few can bind both chaperones. Independent studies suggest that Tah1 interacts with Hsp90, but whether it can also interact with Hsp70/Ssa1 has not been investigated. Amino-acid-sequence alignments suggest that Tah1 is most similar to the TPR2b domain of Hop (Hsp-organizing protein) which when mutated reduces binding to both Hsp90 and Hsp70. Our alignments suggest that there are three TPR-domain motifs in Tah1, which is consistent with the architecture of the TPR2b domain. In the present study we find that Tah1 is specific for Hsp90, and is able to bind tightly the yeast Hsp90, and the human Hsp90alpha and Hsp90beta proteins, but not the yeast Hsp70 Ssa1 isoform. Tah1 acheives ligand discrimination by favourably binding the methionine residue in the conserved MEEVD motif (Hsp90) and positively discriminating against the first valine residue in the VEEVD motif (Ssa1). In the present study we also show that Tah1 can affect the ATPase activity of Hsp90, in common with some other TPR-domain proteins.
Millson
Stefan H
SH
Department of Molecular Biology and Biotechnology, The University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
Vaughan
Cara K
CK
Zhai
Chao
C
Ali
Maruf M U
MM
Panaretou
Barry
B
Piper
Peter W
PW
Pearl
Laurence H
LH
Prodromou
Chrisostomos
C
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism; D020816:Amino Acid Motifs; D002151:Calorimetry; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008024:Ligands; D018832:Molecular Chaperones / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D014461:Ultracentrifugation
D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D008024:Ligands; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; C095973:SSA1 protein, S cerevisiae