AI Article Synopsis
- The study investigates the structural characteristics of the synaptic vesicle protein 2A (SV2A), which is important for the anti-epileptic drug levetiracetam (LEV), using Protein Tomography on mouse brain tissue.
- Two main shapes of SV2A were identified: a compact funnel with a pore-like opening and a V-shaped structure with a cleft, indicating the protein's high flexibility and potential valve-like function.
- The findings suggest that LEV binding does not significantly change the SV2A structure, and the research provides new structural insights that support its function as a transporter, similar to other known transporter proteins.
Article 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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| http://dx.doi.org/10.1016/j.bbrc.2008.07.145 | DOI Listing |
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