Download MendeleyA common structural basis for pH- and calmodulin-mediated regulation in plant glutamate decarboxylase.
Gut, H., Dominici, P., Pilati, S., Astegno, A., Petoukhov, M.V., Svergun, D.I., Grutter, M.G., Capitani, G.(2009) J Mol Biol 392: 334-351
- PubMed: 19580813
- DOI: https://doi.org/10.1016/j.jmb.2009.06.080
- Primary Citation of Related Structures:
3HBX - PubMed Abstract:
Glutamate decarboxylase (Gad) catalyzes glutamate to gamma-aminobutyrate conversion. Plant Gad is a approximately 340 kDa hexamer, involved in development and stress response, and regulated by pH and binding of Ca(2+)/calmodulin (CaM) to the C-terminal domain. We determined the crystal structure of Arabidopsis thaliana Gad1 in its CaM-free state, obtained a low-resolution structure of the calmodulin-activated Gad complex by small-angle X-ray scattering and identified the crucial residues, in the C-terminal domain, for regulation by pH and CaM binding. CaM activates Gad1 in a unique way by relieving two C-terminal autoinhibition domains of adjacent active sites, forming a 393 kDa Gad1-CaM complex with an unusual 1:3 stoichiometry. The complex is loosely packed: thanks to the flexible linkers connecting the enzyme core with the six C-terminal regulatory domains, the CaM molecules retain considerable positional and orientational freedom with respect to Gad1. The complex thus represents a prototype for a novel CaM-target interaction mode. Thanks to its two levels of regulation, both targeting the C-terminal domain, Gad can respond flexibly to different kinds of cellular stress occurring at different pH values.
Organizational Affiliation:
Biochemisches Institut, Universität Zürich, Zürich, Switzerland.
