Intracellular neuronal calcium sensor proteins: a family of EF-hand calcium-binding proteins in search of a function

1999 ◽  
Vol 295 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Karl-Heinz Braunewell ◽  
Eckart D. Gundelfinger
Keyword(s):  
Calcium Binding ◽  
Binding Proteins ◽  
Calcium Binding Proteins ◽  
Calcium Sensor ◽  
Neuronal Calcium Sensor ◽  
Ef Hand ◽  
Sensor Proteins ◽  
Calcium Sensor Proteins

A change-in-hand mechanism for S100 signalling

1998 ◽  
Vol 76 (2-3) ◽  
pp. 324-333 ◽  
Author(s):  
Steven P Smith ◽  
Gary S Shaw
Keyword(s):  
Conformational Change ◽  
Calcium Ion ◽  
Calcium Binding ◽  
Binding Proteins ◽  
Three Dimensional ◽  
Calcium Binding Proteins ◽  
C Terminus ◽  
Ef Hand ◽  
Sensor Proteins ◽  
Binding Loop

S100 proteins are a group of small dimeric calcium-binding proteins making up a large subclass of the EF-hand family of calcium-binding proteins. Members of this family of proteins have been proposed to act as intracellular calcium modulatory proteins in a fashion analogous to that of the EF-hand sensor proteins troponin-C and calmodulin. Recently, NMR spectroscopy has provided the three-dimensional structures of the S100 family members S100A6 and S100B in both the apo- and calcium-bound forms. These structures have allowed for the identification of a novel calcium-induced conformational change termed the change-in-hand mechanism. Helix III of the C-terminal calcium-binding loop changes its helix-helix interactions (or handness) with the remainder of the molecule primarily owing to the reorientation of the backbone in an effort to coordinate the calcium ion. This reorientation of helix III exposes several residues in the C-terminus and linker regions of S100B resulting in the formation of a hydrophobic patch surrounded be a number of acidic residues. This site is the proposed region for protein-protein recognition.Key words: S100, calcium-binding protein, EF-hand, conformational change.

scholarly journals Neuronal calcium sensor proteins are direct targets of the insulinotropic agent repaglinide

2003 ◽  
Vol 375 (1) ◽  
pp. 87-97 ◽  
Author(s):  
Miki OKADA ◽  
Daisuke TAKEZAWA ◽  
Shuji TACHIBANAKI ◽  
Satoru KAWAMURA ◽  
Hiroshi TOKUMITSU ◽  
...  
Keyword(s):  
Protein Family ◽  
Kinase Assay ◽  
Regulatory Function ◽  
Dependent Manner ◽  
Calcium Sensor ◽  
Neuronal Calcium Sensor ◽  
Ef Hand ◽  
Ic50 Values ◽  
Sensor Proteins ◽  
Calcium Sensor Proteins

The NCS (neuronal calcium sensor) proteins, including neurocalcins, recoverins and visinin-like proteins are members of a family of Ca2+-sensitive regulators, each with three Ca2+-binding EF-hand motifs. In plants, lily CCaMK [chimaeric Ca2+/CaM (calmodulin)-dependent protein kinase] and its PpCaMK (Physcomitrella patens CCaMK) homologue are characterized by a visinin-like domain with three EF-hands. In the present study, in an effort to discover NCS antagonists, we screened a total of 43 compounds using Ca2+-dependent drug affinity chromatography and found that the insulinotropic agent repaglinide targets the NCS protein family. Repaglinide was found to bind to NCS proteins, but not to CaM or S100 proteins, in a Ca2+-dependent manner. Furthermore, the drug antagonized the inhibitory action of recoverin in a rhodopsin kinase assay with IC50 values of 400 μM. Moreover, repaglinide tightly bound to the visinin-like domain of CCaMK and PpCaMK in a Ca2+-dependent manner and antagonized the regulatory function of the domain with IC50 values of 55 and 4 μM for CCaMK and PpCaMK respectively. Although both repaglinide and a potent insulin secretagogue, namely glibenclamide, blocked KATP channels with similar potency, glibenclamide had no antagonizing effect on the Ca2+-stimulated CCaMK and PpCaMK autophosphorylation, mediated by their visinin-like domain. In addition, a typical CaM antagonist, trifluoperazine, had no effect on the CCaMK and PpCaMK autophosphorylation. Repaglinide appears to be the first antagonist of NCS proteins and visinin-like domain-bearing enzymes. It may serve as a useful tool for evaluating the physiological functions of the NCS protein family. In addition, since repaglinide selectively targets NCS proteins among the EF-hand Ca2+-binding proteins, it is a potential lead compound for the development of more potent NCS antagonists.

scholarly journals S100A14, a Member of the EF-hand Calcium-binding Proteins, Is Overexpressed in Breast Cancer and Acts as a Modulator of HER2 Signaling

2013 ◽  
Vol 289 (2) ◽  
pp. 827-837 ◽  
Author(s):  
Chengshan Xu ◽  
Hongyan Chen ◽  
Xiang Wang ◽  
Jidong Gao ◽  
Yiqun Che ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Calcium Binding ◽  
Binding Proteins ◽  
Calcium Binding Proteins ◽  
Ef Hand ◽  
Her2 Signaling
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