Calmodulin and Calmodulin Binding Proteins in Dictyostelium: A Primer

Abstract

Dictyostelium discoideum is gaining increasing attention as a model organism for the study of calcium binding and calmodulin function in basic biological events as well as human diseases. After a short overview of calcium-binding proteins, the structure of Dictyostelium calmodulin and the conformational changes effected by calcium ion binding to its four EF hands are compared to its human counterpart, emphasizing the highly conserved nature of this central regulatory protein. The calcium-dependent and -independent motifs involved in calmodulin binding to target proteins are discussed with examples of the diversity of calmodulin binding proteins that have been studied in this amoebozoan. The methods used to identify and characterize calmodulin binding proteins is covered followed by the ways Dictyostelium is currently being used as a system to study several neurodegenerative diseases and how it could serve as a model for studying calmodulinopathies such as those associated with specific types of heart arrythmia. Because of its rapid developmental cycles, its genetic tractability, and a richly endowed stock center, Dictyostelium is in a position to become a leader in the field of calmodulin research.

Structural Aspects and Prediction of Calmodulin-Binding Proteins

“…Recent work on calmodulin’s different binding complexes [ 33 ] has improved our current understanding of the mechanisms that result in the two CaM termini domains exhibiting different characteristics in binding complex modes. Despite this, a comprehensive understanding of exactly how CaM can interact with such a large number of proteins and peptides has yet to be established [ 34 ]. The use of spectral clustering system modeling, which evaluates the extent of binding (e.g., loose binding vs. compact binding) as a function of solvent exposure (hydrophobicity) and interhelical angles, led to three significant discoveries.…”

“…Thus, proteins with IQ motif binding patterns are likely activated in the absence of intracellular calcium ( Figure 1 H), whereas proteins with auto-inhibitory domains are more likely to be activated by high concentrations of calcium. Additional insight into distinctions between apo- and holo-CaM, and interactions with IQ motifs, was recently presented by O’Day et al [ 34 ].…”

Dictyostelium discoideum as a non‐mammalian biomedical model

“…PIP₂ is also important in the develop of seizures in the DOORS syndrome, a disorder involving multiple abnormalities, caused by mutations in the TBC1D24 gene (Fischer et al ., 2016; Frej et al ., 2017). Another key player protein is calmodulin ( calA ), observed in human cells, not only related to heart arrhythmias, but also to epilepsy and delayed neurodevelopment (O'day et al ., 2020). Dictyostelium represents a good model for the study of CalA mutations thanks to its highly conserved structure, haploid genome and the possibility to obtain numerous mutations (O'day et al ., 2020).…”

A Proteomics Analysis of Calmodulin-Binding Proteins in Dictyostelium discoideum during the Transition from Unicellular Growth to Multicellular Development

“…Calmodulin (CaM) is an essential calcium-binding protein that is conserved across eukaryotes [ 4 ]. CaM binds to CaM-binding proteins (CaMBPs) in a calcium-dependent or calcium-independent manner via calmodulin-binding domains (CaMBDs) that include hydrophobic amino acid calcium-dependent motifs or calcium-independent IQ motifs [ 5 , 6 ].…”

“…CaM-dependent events have been well studied in a variety of organisms. One such organism is the social amoeba Dictyostelium discoideum [ 6 , 12 ]. Dictyostelium has a 24-h life cycle that consists of unicellular and multicellular phases [ 13 ].…”