title: Structural and dynamic basis of phospholamban and sarcolipin inhibition of Ca(2+)-ATPase.
abstract: Phospholamban (PLN) and sarcolipin (SLN) are two single-pass membrane proteins that regulate Ca2+-ATPase (SERCA), an ATP-driven pump that translocates calcium ions into the lumen of the sarcoplasmic reticulum, initiating muscle relaxation. Both proteins bind SERCA through intramembrane interactions, impeding calcium translocation. While phosphorylation of PLN at Ser-16 and/or Thr-17 reestablishes calcium flux, the regulatory mechanism of SLN remains elusive. SERCA has been crystallized in several different states along the enzymatic reaction coordinates, providing remarkable mechanistic information; however, the lack of high-resolution crystals in the presence of PLN and SLN limits the current understanding of the regulatory mechanism. This brief review offers a survey of our hybrid structural approach using solution and solid-state NMR methodologies to understand SERCA regulation from the point of view of PLN and SLN. These results have improved our understanding of the calcium translocation process and are the basis for designing new therapeutic approaches to ameliorate muscle malfunctions.
authors: Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors: Nathaniel J
authors: NJ
authors: Traaseth
authors: Kim N
authors: KN
authors: Ha
authors: Raffaello
authors: R
authors: Verardi
authors: Lei
authors: L
authors: Shi
authors: Jarrod J
authors: JJ
authors: Buffy
authors: Larry R
authors: LR
authors: Masterson
authors: Gianluigi
authors: G
authors: Veglia
mesh_terms: D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009124:Muscle Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011510:Proteolipids / Q000737:chemistry* / Q000378:metabolism; D000099211:Phospholamban
chemical_list: D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D009124:Muscle Proteins; D011510:Proteolipids; D000099211:Phospholamban; C077258:sarcolipin