¹H, ¹⁵N and ¹³C backbone resonance assignments of the TPR1 and TPR2A domains of mouse STI1.
Hop/STI1 (Hsp-organizing protein/stress-induced-phosphoprotein 1) is a molecular co-chaperone, which coordinates Hsp70 and Hsp90 activity during client protein folding through interactions with its TPR1 and TPR2A domains. Hsp90 substrates include a diverse set of proteins, many of which have been implicated in tumorigenesis. Over-expression of Hsp90 in cancer cells stabilizes mutant oncoproteins promoting cancer cell survival. Disruption of Hsp90 and its co-chaperone machinery has become a promising strategy for the treatment of cancer. STI1 has also been described as a neurotrophic signaling molecule through its interactions with the prion protein (PrP(C)). Here, we report the (1)H, (13)C and (15)N backbone assignments of the TPR1 and TPR2A domains of mouse STI1, which interact with Hsp70 and Hsp90, respectively. (1)H-(15)N HSQC spectra of TPR2A domain in the presence of a peptide encoding the C-terminal Hsp90 binding site revealed significant chemical shift changes indicating complex formation. These results will facilitate the screening of potential molecules that inhibit STI1 complex formation with Hsp70 and/or Hsp90 for the treatment of cancer and detailed structural studies of the STI1-PrP(C) complex.
Department of Biochemistry, The University of Western Ontario, London, ON N6A 5C1, Canada.
Andrzej
A
Maciejewski
Marco A
MA
Prado
Wing-Yiu
WY
Choy
D000595:Amino Acid Sequence; D000818:Animals; D002247:Carbon Isotopes; D006360:Heat-Shock Proteins / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009587:Nitrogen Isotopes; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011522:Protons
D002247:Carbon Isotopes; D006360:Heat-Shock Proteins; D009587:Nitrogen Isotopes; D011522:Protons; C489791:Stip1 protein, mouse