Calmodulin: Difference between revisions

Calmodulin’s ability to recognize a tremendous range of target proteins is due in large part to its structural flexibility.<ref>{{cite journal | vauthors = Yamniuk AP, Vogel HJ | s2cid = 26585744 | title = Calmodulin's flexibility allows for promiscuity in its interactions with target proteins and peptides | journal = Molecular Biotechnology | volume = 27 | issue = 1 | pages = 33–57 | date = May 2004 | pmid = 15122046 | doi = 10.1385/MB:27:1:33 }}</ref> In addition to the flexibility of the central linker domain, the N- and C-domains undergo open-closed conformational cycling in the Ca²⁺-bound state.<ref name="CYhOa" /> Calmodulin also exhibits great structural variability, and undergoes considerable conformational fluctuations, when bound to targets.<ref name="Tidow_2013">{{cite journal | vauthors = Tidow H, Nissen P | title = Structural diversity of calmodulin binding to its target sites | journal = The FEBS Journal | volume = 280 | issue = 21 | pages = 5551–65 | date = November 2013 | pmid = 23601118 | doi = 10.1111/febs.12296 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Frederick KK, Marlow MS, Valentine KG, Wand AJ | title = Conformational entropy in molecular recognition by proteins | journal = Nature | volume = 448 | issue = 7151 | pages = 325–9 | date = July 2007 | pmid = 17637663 | doi = 10.1038/nature05959 | pmc = 4156320 | bibcode = 2007Natur.448..325F }}</ref><ref>{{cite journal | vauthors = Gsponer J, Christodoulou J, Cavalli A, Bui JM, Richter B, Dobson CM, Vendruscolo M | title = A coupled equilibrium shift mechanism in calmodulin-mediated signal transduction | journal = Structure | volume = 16 | issue = 5 | pages = 736–46 | date = May 2008 | pmid = 18462678 | doi = 10.1016/j.str.2008.02.017 | pmc = 2428103 }}</ref> Moreover, the predominantly hydrophobic nature of binding between calmodulin and most of its targets allows for recognition of a broad range of target protein sequences.<ref name="Tidow_2013" /><ref>{{cite journal | vauthors = Ishida H, Vogel HJ | title = Protein-peptide interaction studies demonstrate the versatility of calmodulin target protein binding | journal = Protein and Peptide Letters | volume = 13 | issue = 5 | pages = 455–65 | date = 2006 | pmid = 16800798 | doi = 10.2174/092986606776819600 }}</ref> Together, these features allow calmodulin to recognize some 300 target proteins<ref name="vCsmX">{{cite web |title=Calmodulin Target Database |url=http://calcium.uhnres.utoronto.ca/ctdb/ |access-date=27 July 2020}}</ref> exhibiting a variety of CaM-binding sequence motifs.

Among the diverse range of defense strategies plants utilize against pathogens, Ca²⁺ signaling is very increasingly common. Free Ca²⁺ levels in the cytoplasm increases in response to a pathogenic infection. Ca²⁺ signatures of this nature usually activate the plant defense system by inducing defense-related genes and the hypersensitive cell death. CaMs, CMLs and CaM-binding proteins are some of the recently identified elements of the plant defense signaling pathways. Several CML genes in [[tobacco]], bean and tomato are responsive to pathogens. CML43 is a CaM-related protein that, as isolated from APR134 gene in the disease-resistant leaves of ''Arabidopsis'' for gene expression analysis, is rapidly induced when the leaves are inoculated with ''[[Pseudomonas syringae]]''. These genes are also found in tomatoes (''Solanum lycopersicum''). The CML43 from the APR134 also binds to Ca²⁺ ions in vitro which shows that CML43 and APR134 are, hence, involved in the Ca²⁺-dependent signaling during the plant immune response to bacterial pathogens.<ref>{{cite journal | vauthors = Chiasson D, Ekengren SK, Martin GB, Dobney SL, Snedden WA | s2cid = 1572549 | title = Calmodulin-like proteins from Arabidopsis and tomato are involved in host defense against Pseudomonas syringae pv. tomato | journal = Plant Molecular Biology | volume = 58 | issue = 6 | pages = 887–897 | date = August 2005 | pmid = 16240180 | doi = 10.1007/s11103-005-8395-x }}</ref> The CML9 expression in ''Arabidopsis thaliana'' is rapidly induced by phytopathogenic bacteria, [[flagellin]] and salicylic acid.<ref>{{cite journal | vauthors = Leba LJ, Cheval C, Ortiz-Martín I, Ranty B, Beuzón CR, Galaud JP, Aldon D | title = CML9, an Arabidopsis calmodulin-like protein, contributes to plant innate immunity through a flagellin-dependent signalling pathway | journal = The Plant Journal | volume = 71 | issue = 6 | pages = 976–89 | date = September 2012 | pmid = 22563930 | doi = 10.1111/j.1365-313x.2012.05045.x | doi-access = free }}</ref> Expression of soybean SCaM4 and SCaM5 in transgenic ''tobacco'' and ''Arabidopsis'' causes an activation of genes related to pathogen resistance and also results in enhanced resistance to a wide spectrum of pathogen infection. The same is not true for soybean SCaM1 and SCaM2 that are highly conserved CaM isoforms. The ''At''BAG6 protein is a CaM-binding protein that binds to CaM only in the absence of Ca²⁺ and not in the presence of it. ''At''BAG6 is responsible for the hypersensitive response of programmed cell death in order to prevent the spread of pathogen infection or to restrict pathogen growth. Mutations in the CaM binding proteins can lead to severe effects on the defense response of the plants towards pathogen infections. Cyclic nucleotide-gated channels (CNGCs) are functional protein channels in the plasma membrane that have overlapping CaM binding sites transport divalent cations such as Ca²⁺. However, the exact role of the positioning of the CNGCs in this pathway for plant defense is still unclear.