8ZLW

Crystal Structure of RDGC IQ motif/dCaM Complex

Summary for 8ZLW

• Entry DOI: 10.2210/pdb8zlw/pdb
• Descriptor: Maltodextrin-binding protein, Calmodulin, Serine/threonine-protein phosphatase rdgC, ... (5 entities in total)
• Functional Keywords: complex serine-threonine phosphatase, protein binding
• Biological source: Escherichia coli #1/H766; More
• Total number of polymer chains: 3
• Total formula weight: 62360.24

Authors

Liu, J.,Ding, Y.Z.,Li, J.C.,Liu, W. (deposition date: 2024-05-21, release date: 2025-04-02, Last modification date: 2025-04-09)

Primary citation

Liu, J.,Wu, C.,Liu, Y.,Chen, Q.,Ding, Y.,Lin, Z.,Pan, L.,Xiao, K.,Li, J.,Liu, Z.,Liu, W.
Structural insights into the dual Ca 2+ -sensor-mediated activation of the PPEF phosphatase family.
Nat Commun, 16:3120-3120, 2025

PubMed Abstract: Serine/threonine-protein phosphatases with EF-hands (PPEFs) are a family of highly conserved proteins implicated in cancer and neuronal degeneration. The initially characterized member, Drosophila melanogaster retinal degeneration C (RDGC) contains a calmodulin (CaM)-interacting extended-IQ motif and a Ca-binding EF-like/EF-hand tandem. However, the molecular regulation of PPEF is poorly understood. In this study, we use cryogenic-electron microscopy to delineate the structures of the RDGC/CaM holoenzyme. In the absence of Ca, CaM and the EF-like/EF-hand tandem allow the extended-IQ motif to block substrate access to the catalytic sites, constituting an auto-inhibitory mechanism. Upon Ca binding, CaM and the EF-like/EF-hand tandem drive drastic conformational changes in the extended-IQ motif to unlock the catalytic sites. This dual Ca-sensor-mediated activation is evolutionarily conserved in mammals. This study provides mechanistic insight into the molecular activation of PPEFs, paving the way for the development of therapeutic strategies for PPEF-related human diseases.

PubMed: 40169586
DOI: 10.1038/s41467-025-58261-z

Experimental method

X-RAY DIFFRACTION (2.2 Å)