The EMBO Journal Vol. 22 No. 13 pp. 3267±3278, 2003 Structural basis of the interaction between RalA and Sec5, a subunit of the sec6/8 complex Shuya Fukai, Hugo T.Matern1, membrane fusion. The tethering step is de®ned as the Junutula R.Jagath1, Richard H.Scheller1 and initial contact of the vesicle via a protein bridge with its Axel T.Brunger2 target compartment and is the critical determinant in the speci®city of membrane fusion. Essential for this tethering Howard Hughes Medical Institute and Departments of Molecular and are multimeric protein complexes that have been shown to Cellular Physiology, Neurology and Neurological Sciences and Stanford Synchrotron Radiation Laboratory, Stanford University, be involved in most, if not all, intracellular traf®cking James H.Clark Center, E300C, 318 Campus Drive, Stanford, CA events (Whyte and Munro, 2002). 94305-5432 and 1Genentech Inc., 1 DNA Way, South San Francisco, The tethering complex for exocytosis at the plasma CA 94080, USA membrane is referred to as the sec6/8 complex or exocyst 2Corresponding author in yeast (TerBush et al., 1996; Kee et al., 1997). This e-mail:
[email protected] hetero-octameric protein complex is composed of the original SEC gene products (Sec3, Sec5, Sec6, Sec8, The sec6/8 complex or exocyst is an octameric protein Sec10, Sec15), plus Exo70 and Exo84. The exocyst complex that functions during cell polarization by components were originally identi®ed in a yeast genetic regulating the site of exocytic vesicle docking to the screen for mutants that are de®cient in the fusion of plasma membrane, in concert with small GTP-binding secretory vesicles with the plasma membrane (TerBush proteins.