Defining the intramembrane binding mechanism of sarcolipin to calcium ATPase using solution NMR spectroscopy

Journal of Molecular Biology
J J BuffyGianluigi Veglia

Abstract

Sarcolipin (SLN) is an integral membrane protein that is expressed in both skeletal and cardiac muscle, where it inhibits SERCA (calcium ATPase) by lowering its apparent Ca2+ affinity in a manner similar to that of its homologue phospholamban (PLN). We use solution NMR to map the structural changes occurring within SLN upon interaction with the regulatory target, SERCA, co-reconstituting the two proteins in dodecylphosphocholine (DPC) detergent micelles, a system that preserves the native structure of SLN and the activity of SERCA, with the goal of comparing these interactions with those of the previously studied PLN-SERCA complex. Our analysis of the structural dynamics of SLN in DPC micelles shows this polypeptide to be partitioned into four subdomains: a short unstructured N terminus (residues 1-6), a short dynamic helix (residues 7-14), a more rigid helix (residues 15-26), and an unstructured C terminus (residues 27-31). Upon addition of SERCA, the different domains behave according to their dynamics, molding onto the surface of the enzyme. Remarkably, each domain of SLN behaves in a manner similar to that of the corresponding domains in PLN, supporting the hypothesis that both SLN and PLN bind SERCA in the same groove and ...Continue Reading

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Citations

Dec 18, 2007·Biochemistry·Nathaniel J TraasethGianluigi Veglia
Nov 17, 2011·Journal of the American Chemical Society·Tiandi ZhuangCharles R Sanders
Mar 31, 2010·The Journal of Physical Chemistry. B·T GopinathGianluigi Veglia
Mar 5, 2013·Nature·Anne-Marie L WintherMorten J Buch-Pedersen
Jul 9, 2011·The Journal of Biological Chemistry·Joseph M AutryDavid D Thomas
Sep 7, 2007·Proceedings of the National Academy of Sciences of the United States of America·Nathaniel J TraasethGianluigi Veglia
Dec 5, 2013·Journal of Cell Communication and Signaling·Giuseppe Inesi, Francesco Tadini-Buoninsegni
Mar 6, 2012·Journal of Structural Biology·Roberta SacchettoGiuseppe Zanotti
Apr 20, 2007·Journal of Molecular and Cellular Cardiology·Poornima BhupathyMuthu Periasamy
Jul 23, 2013·Biochimica Et Biophysica Acta·Lucia BecucciRolando Guidelli
Oct 20, 2007·Biochimica Et Biophysica Acta·Walter R P ScottSuzana K Straus
Oct 6, 2016·The Journal of Physical Chemistry. B·Alysha DickeGianluigi Veglia
Oct 11, 2014·The Journal of Biological Chemistry·Cédric MontignyMarc le Maire
Jul 3, 2018·Frontiers in Physiology·Kevin L Campbell, Alysha A Dicke
Oct 5, 2006·The Journal of Biological Chemistry·Sanjay MallJ Malcolm East
Nov 9, 2019·Heart Failure Reviews·Liu ZhihaoFan Guanwei
Feb 23, 2021·Frontiers in Molecular Biosciences·Thomas BarbotLiliane Mouawad

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