The domains of Hsp70 in the ADP state may be separate and the linker flexible (black line). Hsp70 in the ADP state binds substrate tightly, and Hsp40 dissociates (Hartl and Hayer-Hartl, 2002 Young et al. Hsp70 in the ATP state has the NBD, SBD and the interdomain linker (black bar) closely packed together, and binds substrate poorly. The J domain of a subunit is connected to the central region by a G/F rich linker (gray bar). Substrate can be bound by Hsp40 type 1 proteins, which stimulates Hsp70 ATP hydrolysis through their J domains. The NBD of Hsp110 is light blue, the SBD of Hsp110 is indigo. The orientations of the NBD domains are the same as in A. Colours of the domains are as in A., the linker in dark blue, and substrate in dark gray. 2009) (D) complexed with an Hsp110 co-chaperone (3C7N) (Schuermann et al. 2005) (C) domains separated in the ADP-bound state (2KHO) (Bertelsen et al. (B– D) Structures of Hsp70 two-domain constructs: (B) with the NBD and SBD in contact (1YUW) (Jiang et al. Substrate (dark gray) is bound by subdomain 2 (1NLT) (Li et al. The central region of Hsp40 type 1 proteins has subdomains 1, 2, and 3 arranged in a hooked structure, with the zinc finger motifs at the angle and the main dimerization site at the end of 3. The Hsp40 J domain is elongated with the Hsp70-interacting HPD motif (coloured) at one end (1HDJ) (Qian et al. The Hsp70 substrate binding domain (SBD) has a base and a helical lid, which hold polypeptide substrate (dark gray) between them, in a groove in the base (1DKX) (Zhu et al. A cleft between 1a and 2a may be a regulatory interaction site. The Hsp70 nucleotide-binding domain (NBD) is divided into 2 lobes made up of subdomains 1a, 1b, 2a, and 2b, with ATP (ADP-PO 4 in the structure) bound in the opening (3HSC in PDB) (Flaherty et al. (A) Schematic of Hsp70 and Hsp40 domains with original structures shown below.
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