The integration of membrane proteins into "lipid raft" membrane domains influences many biochemical processes. The intrinsic structural properties of membrane proteins are thought to mediate their partitioning between membrane domains. However, whether membrane topology influences the targeting of proteins to rafts remains unclear. To address this question, we examined the domain preference of three putative raft-associated membrane proteins with widely different topologies: human caveolin-3, C99 (the 99 residue C-terminal domain of the amyloid precursor protein), and peripheral myelin protein 22. We find that each of these proteins are excluded from the ordered domains of giant unilamellar vesicles containing coexisting liquid-ordered and liquid-disordered phases. Thus, the intrinsic structural properties of these three topologically distinct disease-linked proteins are insufficient to confer affinity for synthetic raft-like domains.
Bibliographical noteFunding Information:
This work was supported by U.S. NIH Grants RO1 GM106672 and U54 GM094608. J.P.S. was supported by NIH F32 GM110929, while P.J.B. was supported by F31 NS077681. We thank Ajit Tiwari, Courtney Copeland, and Krishnan Raghunathan for technical assistance, as well as Patricia Bassereau (Institut Curie), Daniel Huster (Universität Leipzig), Sarah Veatch (University of Michigan), Ilya Levental (University of Texas Health Science Center), Andrew Beel (Stanford University), and Catherine Deatherage (Vanderbilt University) for helpful discussions.
© 2016 American Chemical Society.