Figure 7. Evolution of Hsp90 NTD-strap sequences.
Alignments were generated individually for each Hsp90 isoform using a conserved portion of the N-terminal domain and the NTD-strap region. The variable signal sequences for TRAP1 and Grp94 were removed before aligning the 10 divergent sequences. Helix one (H1) of the NTD is annotated above the alignments and begins just after the strictly conserved Phe residue that structurally appears to separate the β-strand region of the NTD from H1. This alignment clearly shows the divergence of both length and sequence within the NTD-strap region and also reveals that residues are more conserved amongst Hsp90 isoforms within H1 and the region following H1. TRAP1 has a much longer strap region than cytosolic Hsp90 and conservation does not pick up until the structural region, as made evident in the TRAP1 crystal structure (Lavery et al., 2014). Both yHsp90 and bHsp90 lack a significant strap sequence and Grp94 clearly has an extended and well-conserved strap region.