The mechanism of calmodulin
Definition of calmodulin
A protein that binds to calcium. Calcium ion is called intracellular second messenger, its concentration changes can regulate cell function, this regulation is mainly through the calmodulin.
Introduction to calmodulin
Calmodulin is a cytosolic protein in eukaryotic cells, consisting of 148 amino acids in a single polypeptide with a relative molecular mass of 16.7 kDa.
calmodulin is a single chain protein with a molecular weight of 16,700 and consists of 148 amino acids. The isoelectric point is 4.3, which is an acidic protein. Different biological sources of calmodulin, its amino acid composition and order or exactly the same, or only a little difference. It is acid resistant, heat resistant, very stable. Calmodulin and the role of many enzymes in the cell. In each of the calmodulin molecules, there are four regions that bind to calcium ions, and their primary structure is very similar. Intracellular calcium levels are usually maintained at about 10-7 molar concentrations. When the external stimulus to intracellular calcium concentration increased rapidly to 10-6 ~ 10-5 molar concentration, the calmodulin that calcium ion binding, conformational changes, increased helicity, as active molecules, and then with the enzyme Combined to make it into a living state. When the calcium ion concentration is less than 10-6 mole concentration, calmodulin is no longer combined with calcium ions, calmodulin and enzymes are restored to no activity. Therefore, it is possible to control many important biochemical reactions in the cell according to the change of calcium ion concentration.
By 1982, the eel and chicken chondrocyte cDNA clones and chicken chondrocyte gene clones had been obtained. According to the first two nucleotide sequence analysis, that their differences are large, but the deduced amino acid sequence is still basically the same. Seven introns were found in the native gene of chickens with a total length of 12 kb. The expression of calmodulin genes is enhanced in the cell division cycle and in cell carcinogenesis.
The composition of calmodulin
The shape of the calmodulin is like a dumbbell, with two spherical ends, which are connected by a long, elastic, helical structure. Each end has two Ca2 domains, each of which can bind to a Ca2, so that a calcium Modified protein can bind 4 Ca2, calmodulin and Ca2 binding after the configuration is quite stable. In the non-stimulated cells, the binding of calmodulin to Ca2 is very low; however, Ca2 binds to calmodulin to form a calcium-calmodulin complex if Ca2 increases in the cells due to stimulation, It will cause changes in calmodulin configuration, and enhance the binding of calmodulin to many effectors.
The mechanism of calmodulin
Calmodulin is a calcium-binding protein that exists in almost all eukaryotic cells. Its role is to be sensitive to any trace of calcium can be captured. Calmodulin is active only after binding to Ca2 +. Thus, hormones can regulate the activity of calmodulin by affecting intracellular Ca2 + concentration changes. The active Ca2 + CaM complex can regulate the metabolic process by interacting with the target enzyme. That is, Ca2 + · CaM complex and target enzymes, such as phosphodiesterase, protein kinase and so on, so that the target enzyme conformation changes (Ca2 + results) and activation, and thus regulate the metabolic process.
After binding to calcium, Calmodulin undergoes a structural change that becomes an activator of some enzymes. And then combined with the enzyme, but also caused by changes in the configuration of the enzyme, so that from the non-active state into the active state, CaM-Ca2 + become the role of these enzymes essential ingredients. Calmodulin participates in many biochemical reactions involving many key enzymes, such as: control information transfer, the second messenger cAMP synthesis and decomposition of adenylate cyclase and phosphodiesterase; in glycogen synthesis and decomposition Provide and store energy phosphorylase kinase and glycogen synthase kinase, protein phosphorylation and dephosphorylation related protein kinase and protein phosphatase, can regulate intracellular calcium concentration, play a calcium pump Ca2 + -ATPase , As well as myosin light chain kinase associated with smooth muscle contraction. Calmodulin is a single chain protein consisting of 148 amino acids with four Ca2 + binding domains, lacking species and tissue specificity. The amino acid composition and arrangement of CaM from different sources, including animals, plants and lower eukaryotes, are essentially the same. In addition, there is no Cys and Pro-OH in the peptide chain, so there is great flexibility in structure.
The biological function of calmodulin
Calmodulin can bind to many different proteins, thus affecting all aspects of cellular function. Calmodulin is involved in the process of life-related activities of inflammatory response, metabolism, apoptosis, muscle contraction, intracellular movement, short and long-term memory, nerve growth and immune response. Some investigators have also found that calmodulin can function in the nucleus, which may be involved in pre-mRNA cleavage and regulation of ribosome polymerization and function play. Many of the calmodulin-binding proteins themselves can not bind to calcium ions, and calcium ions are important second messengers in the cell signaling system, so these calmodulin-binding proteins can use calmodulin as calcium sensors and signaling molecular. Calmodulin can regulate intracellular calcium concentration; in the endoplasmic reticulum, calmodulin can also be used as calcium storage medium. Calmodulin may undergo conformational changes before and after binding to calcium ions, so that specific proteins can be bound to specific reactions. The function of calmodulin can be regulated by transcription and post-translational modifications (eg phosphorylation, acetylation, formylation and proteolysis).