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Zehra, M.

Publications and source records attributed to Zehra, M..

2 recordsLinked to original sources

Calmodulin requires calcium to be a constitutive component of the spindle pole bodies in fission yeast

Although calmodulin is best known as a calcium sensor, it also possesses Ca2+-independent functions, exemplified by the surprising finding that the budding yeast cells remain viable using a calmodulin mutant that cant bind Ca2+ (Geiser et al., 1991). It remains unclear why Ca2+-calmodulin is required in other yeasts or vertebrates. Here, we determined whether such holo-calmodulin is an essential cytoskeletal protein in fission yeast. The S. pombe calmodulin Cam1 was an integral part of both the spindle pole body (SPB) and many actin structures at the equatorial division plane. Two mutants Cam1-2V and -3V, which bound Ca2+ poorly, reduced their localization at the SPBs by 90%. However, their presence in the actin structures remained unchanged. Replacing the endogenous cam1 with cam1-2V cut the number of the Cam1-interacting protein Pcp1 in the SPB by [~]70% and delayed mitosis. In contrast, the assembly and constriction of the cytokinetic ring, which depends on the Cam1-interacting myosins Myo1, Myo51 and Myo52, accelerated. The temperature-sensitive cam1-2V mutant was rescued by either over-expression of pcp1 or deletion of myo1. Thus, Cam1 depends on Ca2+ to promote the SPB assembly and to modulate the actomyosin ring constriction, suggesting holo-calmodulin as an essential cytoskeletal protein.

cell biology↗

Substrate-enhanced filamentation of 3-methylcrotonyl-CoA carboxylase in Legionella pneumophila

3-Methylcrotonyl-CoA carboxylase (MCC) is a biotin-dependent carboxylase that metabolizes the amino acid leucine. MCC is present in bacteria, fungi, plants, and animals. In humans, its overexpression is linked to cancer, and its deficiency is linked to inborn errors of metabolism with severe consequences, so understanding its structure and function has far reaching implications. Here, we explore the MCC from Legionella pneumophila, a pathogenic bacterium with a biphasic life cycle. Our endogenous holoenzyme yielded the highest resolution cryo-EM structure of MCC to date, allowing for identification of protein components by the machine learning tool ModelAngelo, confirmed independently by mass spectrometry. We also observed, for the first time, enhanced filamentation of MCC upon substrate binding. We propose that this filamentation, previously observed in the eukaryotes, but not in bacteria, may be important for cellular processes such as differentiation of life cycle or cell division.

biochemistry↗