Complexins play a critical role in the regulation of neurotransmission by 
regulating SNARE-mediated exocytosis of synaptic vesicles. Complexins can exert 
either a facilitatory or an inhibitory effect on neurotransmitter release, 
depending on the context, and different complexin domains contribute differently 
to these opposing roles. Structural characterization of the central helix domain 
of complexin bound to the assembled SNARE bundle provided key insights into the 
functional mechanism of this domain of complexin, which is critical for both 
complexin activities, but many questions remain, particularly regarding the 
roles and mechanisms of other complexin domains. Recent progress has clarified 
the structural properties of these additional domains, and has led to various 
proposals regarding how they contribute to complexin function. This chapter 
describes spectroscopic approaches used in our laboratory and others, primarily 
involving circular dichroism and solution-state NMR spectroscopy, to 
characterize structure within complexins when isolated or when bound to 
interaction partners. The ability to characterize complexin structure enables 
structure/function studies employing in vitro or in vivo assays of complexin 
function. More generally, these types of approaches can be used to study the 
binding of other intrinsically disordered proteins or protein regions to 
membrane surfaces or for that matter to other large physiological binding 
partners.