Molecular Anatomy of Synaptic Vesicles

A Brownian Dynamics Interpretation of Membrane Protein Clustering

An artist‘s view: The picture shows a plasma membrane with computer-modeled syntaxin-1 clusters as well as several free single molecules. The nanoscale-resolution STED micrograph at the top (blue) reveals real syntaxin clusters as white dots. The cone of light illustrates a photobleaching experiment.

Most plasmalemmal proteins organize in submicrometer-sized clusters whose architecture and dynamics are still enigmatic. With Syntaxin 1 as an example, we applied a combination of far-field optical nanoscopy, biochemistry, fluorescencerecovery after photobleaching (FRAP) analysis, and simulations to show that clustering can be explained by self-organization based on simple physical principles.

On average, the syntaxin clusters exhibit a diameter of 50 to 60 nanometers and contain 75 densely crowded syntaxins that dynamically exchange with freely diffusing molecules. Self-association depends on weak homophilic protein-protein interactions. Our simulations suggest that clustering immobilizes and conformationally constrains the molecules. Moreover, a balance between self-association and crowding-induced steric repulsions is sufficient to explain both the size and dynamics of syntaxin clusters and likely of many oligomerizing membrane proteins that form supramolecular structures.

Exemplary movie of simulated fluorescence recovery after photobleaching.

Publication

Sieber, J. J.; Willig, K. I.; Kutzner, C.; Gerding-Reimers, C.; Harke, B.; Donnert, G.; Rammner, B.; Eggeling, C.; Hell, S. W.; Grubmüller, H. et al.; Lang, T.: Anatomy and dynamics of a supramolecular membrane protein cluster. Science 317 (5841), pp. 1072 - 1076 (2007)
Go to Editor View