scholarly journals Design of Calcium-Binding Proteins to Sense Calcium

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2148 ◽  
Author(s):  
Shen Tang ◽  
Xiaonan Deng ◽  
Jie Jiang ◽  
Michael Kirberger ◽  
Jenny J. Yang

Calcium controls numerous biological processes by interacting with different classes of calcium binding proteins (CaBP’s), with different affinities, metal selectivities, kinetics, and calcium dependent conformational changes. Due to the diverse coordination chemistry of calcium, and complexity associated with protein folding and binding cooperativity, the rational design of CaBP’s was anticipated to present multiple challenges. In this paper we will first discuss applications of statistical analysis of calcium binding sites in proteins and subsequent development of algorithms to predict and identify calcium binding proteins. Next, we report efforts to identify key determinants for calcium binding affinity, cooperativity and calcium dependent conformational changes using grafting and protein design. Finally, we report recent advances in designing protein calcium sensors to capture calcium dynamics in various cellular environments.

2020 ◽  
Vol 21 (4) ◽  
pp. 1210
Author(s):  
Danton H. O’Day ◽  
Ryan J. Taylor ◽  
Michael A. Myre

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.


2020 ◽  
Author(s):  
Francisco Vidal-Domènech ◽  
Gemma Riquelme ◽  
Raquel Pinacho ◽  
Ricard Rodriguez-Mias ◽  
América Vera ◽  
...  

AbstractAlterations in the cortico-cerebellar-thalamic-cortical circuit might underlie the diversity of symptoms in schizophrenia. However, molecular changes in cerebellar neuronal circuits, part of this network, have not yet been fully determined. Using LC-MS/MS, we screened altered candidates in pooled grey matter of cerebellum from schizophrenia subjects who committed suicide (n=4) and healthy individuals (n=4). Further validation by immunoblotting of three selected candidates was performed in two cohorts comprising schizophrenia (n=20), non-schizophrenia suicide (n=6) and healthy controls (n=21). We found 99 significantly altered proteins, 31 of them previously reported in other brain areas by proteomic studies. Transport function was the most enriched category, while cell communication was the most prevalent function. For validation, we selected the vacuolar proton pump subunit 1 (VPP1), from transport, and two EF-hand calcium-binding proteins, calmodulin and parvalbumin from cell communication. All candidates showed significant changes in schizophrenia (n=7) compared to controls (n=7). VPP1 was altered in the non-schizophrenia suicide group and increased levels of parvalbumin were linked to antipsychotics. Further validation in an independent cohort of non-suicidal chronic schizophrenia subjects (n=13) and non-psychiatric controls (n=14) showed that parvalbumin was increased while calmodulin was decrease in schizophrenia. Our findings provide evidence of an dysregulation of calcium-binding proteins in the cerebellum in schizophrenia, suggesting an impact on normal calcium-dependent synaptic functioning of cerebellar circuits. Our study also links VPP1 to suicide behaviours, suggesting a possible impairment in vesicle neurotransmitter refilling and release in these phenotypes.


1994 ◽  
Vol 269 (52) ◽  
pp. 32807-32813
Author(s):  
J A Cox ◽  
I Durussel ◽  
M Comte ◽  
S Nef ◽  
P Nef ◽  
...  

1986 ◽  
Vol 134 (3) ◽  
pp. 1269-1275 ◽  
Author(s):  
Istvan Sohar ◽  
John W.C. Bird ◽  
Pamela B. Moore

Biosystems ◽  
1980 ◽  
Vol 12 (3-4) ◽  
pp. 317-323 ◽  
Author(s):  
L.M.G. Heilmeyer ◽  
U. Jahnke ◽  
M.W. Kilimann ◽  
K.P. Kohse ◽  
J.E. Sperling ◽  
...  

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