High resolution

Module 5: Figure phospholamban and sarcolipin

The structural organization of the sarco/endo-plasmic reticulum Ca2+-ATPase SERCA pump regulators phospholamban (PLN) and sarcolipin (SLN).

Phospholamban (PLN) has two main regions: a C-terminal α-helix that embeds the molecule in the sarcoplasmic reticulum (SR) membrane and an N-terminal cytoplasmic region. The latter has an α-helical region that is connected to the membrane region by a short β-turn. Sarcolipin (SLN) resembles PLN, except that it lacks most of the cytoplasmic domain. The high degree of homology, both conserved residues (grey/green) and identical residues (red), within the transmembrane domain indicates that this region is of particular significance in mediating the ability of these proteins to interact with, and inhibit, SERCA pumps. This inhibitory effect of PLN is reversed by protein kinase A (PKA) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylating Ser-16 and Thr-17 respectively. Reproduced by permission from Macmillan Publishers Ltd: Nat. Rev. Mol. Cell Biol., MacLennan, D.H. and Kranias, E.G. (2003) Phospholamban: a crucial regulator of cardiac contractility. 4:566–577. Copyright (2003); http://www.nature.com/nrm; see MacLennan and Kranias 2003.