Crystal structures of neuronal squid Sec1 implicate inter-domain hinge movement in the release of t-SNAREs

Sec1 molecules associate with t-SNAREs from the syntaxin family in a hetero dimeric complex that plays an essential role in vesicle transport and membr ane fusion. Neuronal rat n-Sec1 has an arch-shaped three-domain structure, which binds syntaxin la through contacts in domains 1 and 3. In both rat nS ec1 and homologous squid s-Sec1, a potential effector-molecule binding-pock et is shaped by residues from domains 1 and 2 and is localized on the oppos ite side of the syntaxin la interaction site. Comparison of several crystal forms of unliganded neuronal squid Sec1 indicates a hinge region between d omains 1 and 2 which allows domain 1 to rotate along a central axis. This m ovement could release syntaxin la upon interaction with a yet unspecified S ec1 effector molecule(s). The binding of an effector protein may also direc tly affect the conformation of the helical hairpin of domain 3, which contr ibutes the other significant syntaxin la binding sites in the rat nSec1/syn taxin la complex structure but adopts multiple conformations in the unligan ded s-Sec1 structures reported here. (C) 2001 Academic Press.