Visualization of SV2A conformations in situ by the use of Protein Tomography
- Department of Molecular and Cellular Sciences, UCB S.A., Granta Park, Great Abington, Cambridge, Cambridgeshire CB1 6GS (United Kingdom)
- UCB S.A., Pharma Sector, Preclinical CNS Research, Braine L'Alleud (Belgium)
- Protein Tomography Lab, Sidec AB, Torshamnsgatan 30A, SE-164 40 Kista (Sweden)
The synaptic vesicle protein 2A (SV2A), the brain-binding site of the anti-epileptic drug levetiracetam (LEV), has been characterized by Protein Tomography{sup TM}. 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.
- OSTI ID:
- 21143915
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 375, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2008.07.145; PII: S0006-291X(08)01464-2; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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