Fig. 8: GrpEL1-mediated nucleotide and substrate release mechanism of human mortalin. | Nature Communications

Fig. 8: GrpEL1-mediated nucleotide and substrate release mechanism of human mortalin.

From: Structural insights into GrpEL1-mediated nucleotide and substrate release of human mitochondrial Hsp70

Fig. 8: GrpEL1-mediated nucleotide and substrate release mechanism of human mortalin.

Upon interaction with a substrate and J-protein, mortalin hydrolyzes ATP and stably interacts with substrate. GrpEL1 interacts asymmetrically with mortalin and facilitates ADP release via interactions at the NBD. Flexibility within the SBD loosens the SBDα subdomain. Following ATP binding in a step-wise mechanism, the NBD dissociates first, which enables the opening of the SBD and subsequent substrate release. Alternatively, ATP binding induces concerted dissociation of mortalin whereby decoupling of SBDα and GrpEL1-B enables substrate release. The intermediate representing the mortalinR126W-GrpEL1WT structure is highlighted in orange.

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