1zll
From Proteopedia
NMR Structure of Unphosphorylated Human Phospholamban Pentamer
Structural highlights
DiseasePPLA_HUMAN Defects in PLN are the cause of cardiomyopathy dilated type 1P (CMD1P) [MIM:609909. Dilated cardiomyopathy is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.[1] [2] Defects in PLN are the cause of familial hypertrophic cardiomyopathy type 18 (CMH18) [MIM:613874. CMH18 is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.[3] FunctionPPLA_HUMAN Phospholamban has been postulated to regulate the activity of the calcium pump of cardiac sarcoplasmic reticulum. Publication Abstract from PubMedContraction and relaxation of heart muscle cells is regulated by cycling of calcium between cytoplasm and sarcoplasmic reticulum. Human phospholamban (PLN), expressed in the sarcoplasmic reticulum membrane as a 30-kDa homopentamer, controls cellular calcium levels by a mechanism that depends on its phosphorylation. Since PLN was discovered approximately 30 years ago, extensive studies have aimed to explain how it influences calcium pumps and to determine whether it acts as an ion channel. We have determined by solution NMR methods the atomic resolution structure of an unphosphorylated PLN pentamer in dodecylphosphocholine micelles. The unusual bellflower-like assembly is held together by leucine/isoleucine zipper motifs along the membrane-spanning helices. The structure reveals a channel-forming architecture that could allow passage of small ions. The central pore gradually widens toward the cytoplasmic end as the transmembrane helices twist around each other and bend outward. The dynamic N-terminal amphipathic helices point away from the membrane, perhaps facilitating recognition and inhibition of the calcium pump. The structure of phospholamban pentamer reveals a channel-like architecture in membranes.,Oxenoid K, Chou JJ Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):10870-5. Epub 2005 Jul 25. PMID:16043693[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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