It has become increasingly evident that G-protein coupled receptors (GPCRs) associate with each other in membranes to form (homo- or hetero-) oligomeric complexes and that these oligomers broaden the range of cell signaling. A better understanding of the factors that drive oligomerization would potentially be key for understanding receptor function. To pursue such ambitious goals of addressing structure-function relationship of GPCR oligomers in the future, a number of technological and methodological developments are necessary, together with a viable GPCR model to address basic questions regarding the functional impact of oligomerization, the lipid membrane environment, and hydration. We choose the bacterial proteorhodopsin (PR), a 7-helical transmembrane protein, that serve as an excellent system to test new biophysical tools to determine their oligomeric state and structure in detergent and lipid membranes, as well as to map out its function by multiple methods, including pKA measurements, time-resolved UV/vis absorption spectroscopy of its retinal center, as well as the light-triggered movement of its E-F loop connecting the 5th and 6th a-helix. I will also present advances we made in developing electron paramagnetic resonance (EPR) methods of Gd3+ spin-based labels to sensitively capture multiple distances in the 2-6 nm regime and Overhauser dynamic nuclear polarization to directly map out membrane and protein surface hydration dynamics. The combination of new and established tools permits us to pursue important questions: (1) What is the oligomeric state of the 7TM PR in lipid membranes? (2) Do lipid membrane composition, dynamics and hydration tune oligomerization? (3) What is the functional role of oligomerization observed for PR? (4) Is oligomerization a dominant factor in function tuning over that of surfactant composition or lipid membrane properties? I will address these questions in my presentation.

Functional consequences of membrane protein oligomerization illustrated with proteorhodopsin

254th National Meeting (2017)

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