Interaction of membrane proteins and lipids with solubilizing detergents

Detergents are indispensable in the isolation of integral membrane proteins from biological membranes to study their intrinsic structural and function al properties. Solubilization involves a number of intermediary states that can be studied by a variety of physicochemical and kinetic methods; it usu ally starts by destabilization of the lipid component of the membranes, a p rocess that is accompanied by a transition of detergent binding by the memb rane from a noncooperative to a cooperative interaction already below the c ritical micellar concentration (CMC). This leads to the formation of membra ne fragments of proteins and lipids with detergent-shielded edges. In the f inal stage of solubilization membrane proteins are present as protomers, wi th the membrane inserted sectors covered by detergent. We consider in detai l the nature of this interaction and conclude that in general binding as a monolayer ring, rather than as a micelle, is the most probable mechanism. T his mode of interaction is supported by neutron diffraction investigations on the disposition of detergent in 3-D crystals of membrane proteins. Final ly, we briefly discuss the use of techniques such as analytical ultracentri fugation, size exclusion chromatography, and mass spectrometry relevant for the structural investigation of detergent solubilized membrane proteins. ( C) 2000 Elsevier Science B.V. All rights reserved.