| Autor: |
Gregory T. Tietjen, Mark L. Schlossman, James E. Crooks, Kathleen D. Cao, Benoît Roux, Binhua Lin, Charles T.R. Heffern, Ernesto Vargas, Ka Yee C. Lee, Erin J. Adams, Mati Meron, Chiu-Hao Chen |
| Rok vydání: |
2013 |
| Předmět: |
|
| Zdroj: |
Biophysical Journal. 104(2) |
| ISSN: |
0006-3495 |
| DOI: |
10.1016/j.bpj.2012.11.2016 |
| Popis: |
The immune system recognizes a vast array of chemical signatures as antigens although historically most research has focused more exclusively on protein/protein recognition. More recently it has been appreciated that lipid membranes can also provide important immunological signals as demonstrated in both phosphatidylserine (PS) recognition in apoptotic cell clearance and transient PS exposure in T Cell activation. Despite the clear immunological importance of PS exposure and recognition, there remain very few molecular details regarding the mechanisms of PS membrane recognition. Even more fundamentally, it remains unclear if all PS exposing membranes are immunologically equal or if there exists a sensitivity to additional membrane properties beyond simply the presence or absence of PS. To address this gap in our understanding we have made use of a novel combination of biophysical and biochemical techniques to elucidate the molecular mechanisms by which Tim4 (an immune related PS receptor) recognizes PS containing membranes. Tryptophan fluorescence binding assays have revealed that Tim4 binding is sensitive to membrane PS composition suggesting that there is more to the story than a single PS to single protein interaction. By utilizing a combination of x ray reflectivity measurements to determine membrane bound protein orientation and depth of penetration, as well as molecular dynamics simulations to support the experimental results, we have developed a protein/membrane binding model that provides structural evidence to explain the unique complexities of Tim4 mediated PS membrane recognition. Most significantly, these results provide a standard against which other immunologically related PS receptors can be compared, thereby allowing us to begin to address the more fundamental question of just how important lipid membrane recognition is for our bodies' immunological defense mechanisms. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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