PubMed HealthSearch

PubMed · 1505006

Yeast calmodulin: structural and functional elements essential for the cell cycle.

Abstract

The budding yeast Saccharomyces cerevisiae is a suitable organism for studying calmodulin function in cell proliferation. Genetic studies in yeast demonstrate that vertebrate calmodulin can functionally replace yeast calmodulin. In addition, expression of half of the yeast calmodulin molecule is found to be sufficient for cell growth. Characterization of conditional-lethal mutants of yeast calmodulin as well as the intracellular distribution of calmodulin have suggested that at least two cell cycle steps require calmodulin function. One is nuclear division and the other is the maintenance of cell polarity. A current focus is to understand which kinds of target proteins are involved in mediating the essential functions of yeast calmodulin in these processes. Thus far, three yeast enzymes whose activity is regulated by calmodulin have been identified.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Y Ohya, Y Anraku. Yeast calmodulin: structural and functional elements essential for the cell cycle.. https://doi.org/10.1016/0143-4160(92)90057-y

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Cryo-EM structure of soluble VPS13C suggests its regulation by a conformational switch and by calmodulin.

Bridge-like lipid transfer proteins (BLTPs) play fundamental roles in cellular lipid redistribution between organellar membranes. They comprise bridge domains spanning organelles at contact sites that allow lipids to transit through the cytosol between adjacent membranes. The assembly of BLTPs into complexes with adaptor proteins enables lipid transfer. To address the mechanisms underlying the assembly and regulation of BLTP complexes, we used cryo-EM to resolve the structure of one such BLTP, the Parkinson's disease protein VPS13C, at near-atomic resolution. The structure identifies a lipid-transfer-nonpermissive conformation, in which the built-in C-terminal VAB adaptor module blocks the end of the lipid transfer bridge, interfering with lipid delivery. We also identify calmodulin (CaM), central to calcium signaling, as a constitutive VPS13C interactor. Calcium induces conformational changes in the VPS13C-CaM complex, suggesting calcium regulation of VPS13 function. Altogether, this structure of intact VPS13C serves as a starting point for understanding its regulation and that of other VPS13 proteins.

Calmodulin

Calmodulin D133H Disrupts Cav1.2 and Kv7.1 Regulation to Prolong Cardiac Action Potentials in Long QT Syndrome.

Calmodulin (CaM) plays a central role in cardiac excitation-contraction coupling by regulating ion channels, including the L-type calcium (Ca2+) channel Cav1.2 and the voltage-gated potassium (K+) channel Kv7.1. Mutations in CaM are linked to severe arrhythmogenic disorders such as Long QT syndrome (LQTS), yet the molecular mechanisms remain incompletely understood. Here, we investigate the structural and functional consequences of the arrhythmia-associated CaM variant D133H. Biophysical analysis revealed that D133H destabilises Ca2+ binding at the C-terminal lobe of CaM, altering its Ca2+-dependent conformational changes. Electrophysiological recordings demonstrated that CaM D133H impairs Ca2+-dependent inactivation (CDI) of Cav1.2, prolonging Ca2+ influx, while also reducing activation of Kv7.1, thereby limiting repolarising K+ currents. Together, these dual defects converge to prolong action potential duration, providing a mechanistic basis for arrhythmogenesis in LQTS. Our findings establish that CaM D133H perturbs both Ca2+ and K+ channel regulation, highlighting a shared pathway by which calmodulinopathy mutations disrupt cardiac excitability.

Calmodulin

Regression analysis of factorially designed trials--a logical approach to protein crystallization.

The specific composition of the mother liquor that induces the formation of protein crystal is usually quoted as the 'best condition' for crystallization. However, very little is described about how these conditions were determined. These missing and non-reported details would certainly lead to a better understanding of why a specific purified protein does not crystallize, and why crystallization seems to be a totally unpredictable enterprise. In this paper, it is shown that a simple regression model applied to a set of factorially designed experiments (comprising successful and failed experiments) is a useful tool for the analysis of crystallization outcomes. The applications of this approach to the proteins lysozyme and calmodulin yielded results that did not substantially differ from published accounts. When this procedure is applied to myelin basic protein (MBP) and to a MBP and calmodulin complex no crystals formed, which would suggest that neither is easy to crystallize. In summary, factorial design and regression analysis can be an important methodological approach for crystallizing proteins.

Calmodulin