Dimerization of Human Drebrin-like Protein Governs Its Biological Activity.

Drebrin-like protein (DBNL) is a multidomain F-actin-binding protein, which also interacts with other molecules within different intracellular pathways. Here, we present quantitative measurements on the size and conformation of human DBNL. Using dual-focus fluorescence correlation spectroscopy, we determined the hydrodynamic radius of the DBNL monomer. Native gel electrophoresis and dual-color fluorescence cross-correlation spectroscopy show that both endogenous DBNL and recombinant DBNL exist as dimers under physiological conditions. We demonstrate that C-terminal truncations of DBNL downstream of the coiled-coil domain result in its oligomerization at nanomolar concentrations. In contrast, the ADF-H domain alone is a monomer, which displays a concentration-dependent self-assembly. In vivo FLIM-FRET imaging shows that the presence of only actin-binding domains is not sufficient for DBNL to localize properly at the actin filament inside the cell. In summary, our work provides detailed insight into the structure-function relationship of human drebrin-like protein.

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