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Invisible detergents for structure determination of membrane proteins by small‐angle neutron scattering
Author(s) -
Midtgaard Søren Roi,
Darwish Tamim A.,
Pedersen Martin Cramer,
Huda Pie,
Larsen Andreas Haahr,
Jensen Grethe Vestergaard,
Kynde Søren Andreas Røssell,
SkarGislinge Nicholas,
Nielsen Agnieszka Janina Zygadlo,
Olesen Claus,
Blaise Mickael,
Dorosz Jerzy Józef,
Thorsen Thor Seneca,
Venskutonytė Raminta,
Krintel Christian,
Møller Jesper V.,
Frielinghaus Henrich,
Gilbert Elliot Paul,
Martel Anne,
Kastrup Jette Sandholm,
Jensen Poul Erik,
Nissen Poul,
Arleth Lise
Publication year - 2018
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14345
Subject(s) - deuterium , neutron scattering , chemistry , membrane , membrane protein , micelle , neutron , small angle neutron scattering , scattering , crystallography , isotope , integral membrane protein , neutron diffraction , analytical chemistry (journal) , chromatography , biochemistry , physics , optics , nuclear physics , crystal structure , organic chemistry , aqueous solution
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 (D 2 O) 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 Ca 2+ 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.