Hydrogen exchange mass spectrometry of membrane proteins in phospholipid bilayer nanodisks provides a controllable way to examine the conformation of membrane proteins in nativelike conditions, according to a study by chemists at Boston’s Northeastern University and the University of North Carolina, Chapel Hill (Anal. Chem., DOI: 10.1021/ac100962c). Structural information is difficult to obtain for membrane proteins because they don’t crystallize easily. So John R. Engen, Kasper D. Rand, and coworkers use phospholipid bilayer nanodisks to mimic the cellular environment of membrane proteins. They expose a nanodisk loaded with a membrane protein to deuterated water for defined lengths of time. After quenching the reaction, they use MS of the digested proteins to determine where deuterium was incorporated. Using the 94-kilodalton γ-glutamyl carboxylase as an example, they observed deuterium incorporation in 71 peptides, indicating that these parts of the membrane protein are accessible to solvent. The work “should provide incentive for many to use the same approach to solve interesting questions about membrane protein structure and topology in bilayer structures,” says Stephen G. Sligar of the University of Illinois, Urbana-Champaign, who invented the nanodisks.