Fig. 4: Second site mutations rescue the hHsp90β-EA growth defect and their effects are conserved.
From: Nucleotide exchange is sufficient for Hsp90 functions in vivo
a Suppressors of the hHsp90β-EA growth defect are in or near the ATP binding pocket. T179 (yellow) is next to D88 (orange) and interacts with the adenosine ring of bound nucleotides (white). E384 (red) is in the M domain but comes very close to the lid structure (cyan) in closed Hsp90. E42 (blue) and Mg++ (gray sphere) are also shown for reference. hHsp90β structure is from PDB ID 5fwk51. b T179A and E384K improved the ability of hHsp90β-EA to support viability of S. cerevisiae. c EK improved the growth of S. cerevisiae cells expressing hHsp90α-EA but not SpHsp90-EA. TA modestly rescued SpHsp90-EA but not hHsp90α-EA. d TA and EK rescued the EA slow growth defect of S. cerevisiae cells expressing EA. Cells expressing EAEK grew as fast as cells expressing wild type Hsp82. Bars are the average doubling times of three biological replicates (circles) and the error bars are the standard deviation. Source data are provided as a Source Data file. e In Sz. pombe, the effect of TA and EK on improving growth of human Hsp90s was similar as in S. cerevisiae, while the suppressors did not improve growth of Sz. pombe cells expressing EA versions of S. cerevisiae Hsp90s.
