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  • Title: Visualization of SV2A conformations in situ by the use of Protein Tomography.
    Author: Lynch BA, Matagne A, Brännström A, von Euler A, Jansson M, Hauzenberger E, Söderhäll JA.
    Journal: Biochem Biophys Res Commun; 2008 Oct 31; 375(4):491-5. PubMed ID: 18692481.
    Abstract:
    The synaptic vesicle protein 2A (SV2A), the brain-binding site of the anti-epileptic drug levetiracetam (LEV), has been characterized by Protein Tomography. We identified two major conformations of SV2A in mouse brain tissue: first, a compact, funnel-structure with a pore-like opening towards the cytoplasm; second, a more open, V-shaped structure with a cleft-like opening towards the intravesicular space. The large differences between these conformations suggest a high degree of flexibility and support a valve-like mechanism consistent with the postulated transporter role of SV2A. These two conformations are represented both in samples treated with LEV, and in saline-treated samples, which indicates that LEV binding does not cause a large-scale conformational change of SV2A, or lock a specific conformational state of the protein. This study provides the first direct structural data on SV2A, and supports a transporter function suggested by sequence homology to MFS class of transporter proteins.
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