Molecular mechanism of omega-3 fatty acid transport into the brain

NARRATIVE This application will provide a molecular-level understanding of how the essential omega-3 fatty acid docosahexaenoic acid (DHA) traverses the blood-brain barrier and eye-brain barrier to enter into the brain and eye, respectively. We have determined the structure of MSFD2A, the transporter responsible for this crucial step, using cutting-edge single-particle cryo-electron microscopy, and here propose to contribute structures in different conformations, which, together with biochemical assays we have developed in a collaborative effort, will allow us to test and validate structure-based functional hypotheses.