Group:MUZIC:Calcineurin

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Contents 1 Calcineurin 2 Calcineurin in the muscle cells 3 Calcineurin interactions and their physiological role 4 Further Readings 5 References

Calcineurin

Calcineurin is a calcium calmoduline dependent phosphatase present in many different type of cells. This phosphatase has been described to be mainly localized in the cyoplasma where dephosphorylates members of the nuclear factor of activated T-cell (NFAT) family of transcription factors. As a result NFAT is translocated to the nuclei and activates target genes that promote cell proliferation.^[1]

spinqualitylabelsall models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Structure spinqualitylabelsall models Insert caption here Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image The calcium/calmodulin-dependent phosphatase calcineurin is composed by two chains: chain A, (CnA) which is the catalytic subunit and chain B(CnB) confers calcium sensitivity. [2]Those two subunits are tighlty bound and they only disociate under denaturant conditions.[3] The interaction between CnB and CnA is essential for the phosphatase activity of Calcineurin and while it is known that calcium binding to CnB promotes the interaction CnB with CnA, the mechanism whereby it goes is not yet fully understood. [4] CnA contains a followed by an alpha-helical region which forms the and an Calmodulin-binding region. In the C-terminal region of CnA there are 18 residues considered as an that lies over the substrate binding cleft in the catalytic domain. On the other hand, CnB is a 168 polipeptide chain that belongs to the EF-hand calcium binding protein family. this subunit is composed of two lobes with two calcium ions bound by in each lobe. [5]

Calcineurin in the muscle cells

This calcium/calmodulin-dependent protein serine/threonine phosphate is localized in the nucleus and in the Z-disc of muscle fibers. Its activity is controled by calcium signals that lead to remodeling of skeletal and cardiac muscle in response to physiological and pathological stimuli.

Calcineurin interactions and their physiological role

Further Readings

References

1. ↑ Rao A, Luo C, Hogan PG. Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol. 1997;15:707-47. PMID:9143705 doi:10.1146/annurev.immunol.15.1.707
2. ↑ Kissinger CR, Parge HE, Knighton DR, Lewis CT, Pelletier LA, Tempczyk A, Kalish VJ, Tucker KD, Showalter RE, Moomaw EW, et al.. Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex. Nature. 1995 Dec 7;378(6557):641-4. PMID:8524402 doi:http://dx.doi.org/10.1038/378641a0
3. ↑ Kissinger CR, Parge HE, Knighton DR, Lewis CT, Pelletier LA, Tempczyk A, Kalish VJ, Tucker KD, Showalter RE, Moomaw EW, et al.. Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex. Nature. 1995 Dec 7;378(6557):641-4. PMID:8524402 doi:http://dx.doi.org/10.1038/378641a0
4. ↑ Stemmer PM, Klee CB. Dual calcium ion regulation of calcineurin by calmodulin and calcineurin B. Biochemistry. 1994 Jun 7;33(22):6859-66. PMID:8204620
5. ↑ Kissinger CR, Parge HE, Knighton DR, Lewis CT, Pelletier LA, Tempczyk A, Kalish VJ, Tucker KD, Showalter RE, Moomaw EW, et al.. Crystal structures of human calcineurin and the human FKBP12-FK506-calcineurin complex. Nature. 1995 Dec 7;378(6557):641-4. PMID:8524402 doi:http://dx.doi.org/10.1038/378641a0