Molecular mechanism for differential recognition of membrane phosphatidylserine by the immune regulatory receptor Tim4
Abstract
Structural immunology employs static, atomic-level representations to uncover the molecular mechanisms by which immune receptors sensitively discern infection and disease. Lipid membranes, particularly those exposing phosphatidylserine lipids, are now understood to be important signals in various aspects of immune regulation. However, the dynamic nature of lipid membranes makes the standard tools of structural immunology poorly suited to these systems, leaving a large gap in our understanding. Here we implement a suite of multidisciplinary tools to demonstrate, for the first time to the authors' knowledge, a mechanism for sensitivity of an immune regulatory receptor (Tim4) to the membrane context of phosphatidylserine exposure. These findings uncover new aspects of Tim4's recognition properties and, perhaps more significantly, provide a methodology for obtaining atomic-level detail in membrane recognition.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- April 2014
- DOI:
- 10.1073/pnas.1320174111
- Bibcode:
- 2014PNAS..111E1463T