Phospholamban, calcium pump

Activity is modulated by other proteins present in the membrane. These include a glycoprotein (MW 53 000) which stimulates ATPase activity 138 a 60 000 molecular weight protein, which is phosphorylated in a calmodulin-dependent fashion, affects accumulation of calcium 139 while the activity of the enzyme is affected by an endogenous kinase and phosphatase which phosphorylates and dephosphorylates the protein.140 Phospholamban is a proteolipid (MW 22 000) in cardiac SR which undergoes both cyclic AMP-dependent and calcium-calmodulin-dependent phosphorylation,141 but at different sites. All these proteins are probably involved in regulating the activity of the calcium pump. 

Phospholamban is a homopentameric membrane protein involved in muscle contraction through regulation of the calcium pump in cardiac muscle cells. The stmcture of the unphospho-rylated protein solved in DPC micelles reveals a symmetric pentamer of phospholamban monomers (Fig. 2g) stabilized by leucine/isoleucine zipper motifs along the transmembrane domains (51). Notably, another stmcture was produced for phospholamban (Fig. 2h) that used a variant of the traditional simulated annealing and molecular dynamics protocol that reduced the chances of entrapment in local minima (52). 

The sarcoplasmic reticulum (SR) calcium pump together with phosphorylation of specific proteins, has an important role in myocardial contraction and relaxation. Phospholamban, a 20-24 kDa proteolipid, is phosphorylated by cAMP-dependent protein kinase as well as calmodulin-dependent protein kinase. Phosphorylation of this protein results in stimulation of Ca +-ATPase and Ca + transport by the SR (Scheme 4.1.1). ... 

Zamoon J, Nitu F, Karim C, Thomas DD, Veglia G (2005) Mapping the interaction surface of a membrane protein unveiling the conformational switch of phospholamban in calcium pump regulation. Proc Natl Acad Sci USA 102 4747 752... 

Sarcoplasmic calcium ATPase this enzyme utilizes the energy gained from hydrolysis of ATP to pump calcium from the cytosol into the stores of the sarcoplasmic reticulum. Its activity is negatively regulated by the closely associated protein phospholamban, and this inhibition is relieved upon phosphorylation of phospholamban by protein kinase A (PKA). 

One should be cautious, however, to extrapolate such quantitative data to all smooth muscle types or even to similar ones of other species because of the heterogeneity of smooth muscle. For instance, Stehno-Bittel and Sturek (1992) found evidence for preferential release of Ca + from the ER toward the sarcolem-ma in bovine but not in porcine coronary artery. The ER also differs between different smooth muscles in the expression of different types of calcium-buffering proteins (Raeymaekers etal., 1993) and of the regulator protein phospholamban (see Section V). Furthermore, the data of Eggermont et al. (1988) indicate that the ratio of the number of ER and PM pump proteins also varies considerably between different smooth muscle types. 

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