Computational Modeling of Allosteric Regulation in the Hsp90 Chaperones: A Statistical Ensemble Analysis of Protein Structure Networks and Allosteric Communications
Figure 1
The Architecture and Structural Motifs of the Hsp90 Dimers.
The topology and conserved structural regions of the Hsp90 dimer are shown for the crystal structure of yeast ATP-Hsp90 [55] (A), and the crystal structure of ADP-HtpG [56] (B). The structures are shown in a ribbon representation and main structural elements of the Hsp90 dimer are annotated. The Hsp90 domains are colored as follows: Hsp90-NTD (in green), Hsp90-MD (in blue), and Hsp90-CTD (in red). (A) Structural regions of the ATP-Hsp90 dimer. The lid residues 95–123 are highlighted in black sticks. The catalytic loop (371-SEDLPLNLSREMLQQ-385) with a key catalytic residue R-380 is depicted in sticks. The ATP molecules are shown in spheres colored by atoms. The three-helix bundle elements are shown in blue ribbons according to the Hsp90-MD coloration (helix 1: residues 386–408; helix 2: residues 412–431; helix3: residues 435–442) links the inter-domain regions. The inter-domain hinge residues are shown blue spheres. The NTD-MD hinge region (residues 376-LNLSREML-383) also includes catalytic R380. The MD-CTD hinge site includes residues 426-KLGVHE-431. (B) Structural regions of the ADP-HtpG dimer. The functionally important lid region of HtpG (residues 100–126 according to [56]) is highlighted in black sticks as in (A). The ATP molecules are shown in spheres colored by atoms. The three-helix bundle elements are shown in blue ribbons according to the Hsp90-MD coloration (helix 1: residues 336–366 where R336 is the catalytic residue; helix2: residues 368–388; helix 3: residues 393–399). The inter-domain hinge residues are shown in blue spheres. The NTD-MD inter-domain hinge site in HtpG is formed by conserved residues 332-LNVSREIL-339 that contain catalytic R336, and the MD-CTD hinge region includes residues 378-FGLVLKE-384.