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Vol. 59, Issue 5, 1243-1248, May 2001
2
Subunits
Structure and
Gabapentin Binding
Institut für Pharmakologie und Toxikologie der Technischen
Universität München, München, Germany
High-voltage activated calcium channels are modulated by a series of
auxiliary proteins, including those of the 
2
family. Until recently, only a single 2 subunit was known,
but two further members, 2-2 and -3, have since been
identified. In this study, the structure of these two novel subunits
has been characterized and binding of the antiepileptic drug gabapentin
investigated. Using antibodies directed against the amino terminal
portion of the proteins, the gross structure of the subunits could be
analyzed by Western blotting. Similar to 2-1, both
2-2 and -3 subunits consist of two proteins
a larger
2 and a smaller that can be separated by reduction.
The subunits are also highly N-glycosylated with
approximately 30 kDa of their mass consisting of oligosaccharides. 2-1 was detected in all mouse tissues studied,
whereas 2-2 was found at high levels in brain and
heart. The 2-3 subunit was observed only in brain.
2-1 and 2-2, but not
2-3, were found to bind gabapentin. The
Kd value of gabapentin binding to 2-2 was 153 nM compared with the higher affinity
binding to 2-1 (Kd = 59 nM).
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