Invisible Detergents for Structure Determination of Membrane Proteins by Small-angle Neutron Scattering

Søren Roi Midtgaard*, Tamim A. Darwish, Martin Cramer Pedersen, Pie Huda, Andreas Haahr Larsen, Grethe Vestergaard Jensen, Søren Andreas Røssell Kynde, Nicholas Skar-Gislinge, Agnieszka Janina Zygadlo Nielsen, Claus Olesen, Mickael Blaise, Jerzy Józef Dorosz, Thor Seneca Thorsen, Raminta Venskutonytė, Christian Krintel, Jesper V. Møller, Henrich Frielinghaus, Elliot Paul Gilbert, Anne Martel, Jette Sandholm KastrupPoul Erik Jensen, Poul Nissen, Lise Arleth

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review


A novel and generally applicable method for determining structures of membrane proteins in solution via small-angle neutron scattering (SANS) is presented. Common detergents for solubilizing membrane proteins were synthesized in isotope-substituted versions for utilizing the intrinsic neutron scattering length difference between hydrogen and deuterium. Individual hydrogen/deuterium levels of the detergent head and tail groups were achieved such that the formed micelles became effectively invisible in heavy water (D2O) when investigated by neutrons. This way, only the signal from the membrane protein remained in the SANS data. We demonstrate that the method is not only generally applicable on five very different membrane proteins but also reveals subtle structural details about the sarco/endoplasmatic reticulum Ca2+ ATPase (SERCA). In all, the synthesis of isotope-substituted detergents makes solution structure determination of membrane proteins by SANS and subsequent data analysis available to nonspecialists.

Original languageEnglish
JournalFEBS Journal
Issue number2
Pages (from-to)357-371
Number of pages15
Publication statusPublished - Jan 2018
Externally publishedYes


  • Contrast matching
  • Deuteration
  • Membrane proteins
  • SANS
  • Small-angle neutron scattering

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