Structure and function of longin SNAREs

Abstract

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins constitute the core membrane fusion machinery of intracellular transport and intercellular communication.A little more than ten years ago, it was proposed that the long N-terminal domain of a subset of SNAREs, henceforth called the longin domain, could be a crucial regulator with multiple functions in membrane trafficking. Structural, biochemical and cell biology studies have now produced a large set of data that support this hypothesis and indicate a role for the longin domain in regulating the sorting and activity of SNAREs. Here, we review the first decade of structurefunction data on the three prototypical longin SNAREs: Ykt6, VAMP7 and Sec22b. We will, in particular, highlight the conserved molecular mechanisms that allow longin domains to fold back onto the fusioninducing SNARE coiled-coil domain, thereby inhibiting membrane fusion, and describe the interactions of longin SNAREs with proteins that regulate their intracellular sorting. This dual function of the longin domain in regulating both the membrane localization and membrane fusion activity of SNAREs points to its role as a key regulatory module of intracellular trafficking.

Endoplasmic reticulum stress signalling – from basic mechanisms to clinical applications

“…It also comes in contact with the plasma membrane (PM), an interaction regulated by proteins like stromal interaction molecule 1 in the ER and calcium release‐activated calcium channel protein 1 in the PM which are controlled by Ca 2+ levels . Vesicle‐trafficking protein SEC22b (SEC22b) and vesicle‐associated membrane protein 7 are also involved in the stabilization of ER‐PM contacts and PM expansion . The ER also interacts with endosomes and is tethered by StAR‐related lipid transfer protein 3 and StAR‐related lipid transfer protein 3 , which also contribute to cholesterol maintenance in endosomes .…”

“…The transcription factor ATF6, which belongs to an extensive family of leucine zipper proteins , is encoded in humans by two different genes: ATF6A for ATF6α and ATF6B for ATF6β . After its activation in the ER and export to the Golgi, it is cleaved by the two Golgi‐resident proteases membrane bound transcription factor peptidase, site 1 (MBTPS1) and MBTPS1, releasing a fragment of ~ 400 amino acids corresponding to ATF6 cytosolic N‐terminal portion (ATF6f).…”

SolubleN-ethylmaleimide-sensitive factor attachment protein receptors required duringTrypanosoma cruziparasitophorous vacuole development

“…VAMP3 located on early and recycling endosomes and VAMP7 on late endosomes and post‐Golgi secretory vesicle. VAMP3 is proteolysed by tetanus neurotoxin (TeNT), like its neuronal counterparts VAMP1 and VAMP2, whereas VAMP7 is resistant to TeNT (Proux‐Gillardeaux, Rudge, & Galli, ) and has a regulatory amino‐terminal extension called longin domain (Daste, Galli, & Tareste, ). VAMP3 regulates endosomal receptor recycling (Galli et al, ; Breton et al, ).…”

Multiple Types of Guanine Nucleotide Exchange Factors (GEFs) for Rab Small GTPases

“…Longin domains were originally characterized as an N-terminal conserved domain of a vesicle SNARE, e.g., VAMP7 (also called TI-VAMP) (Filippini et al, 2001), and some of them are now recognized as an interacting domain for small GTPases (e.g., Rabs and Rags). Interestingly, a number of uncharacterized longin-domain-containing proteins (named longin proteins) have been identified in eukaryotes (reviewed in De Franceschi et al, 2014;Daste et al, 2015). It is therefore possible that such uncharacterized longin proteins (e.g., DENN-related protein; see next section) function as In general, a GDP-bound form of Rab is present in the cytosol through interaction with GDI (top).…”

“…However, the longin-like fold has recently been shown to be a common feature of several GEFs, including DENN proteins, the BLOC-3 (Mon1-Ccz1) complex, and the TRAPP complexes). Thus, future investigations of as yet uncharacterized longin proteins may yield important clues that will enable identification of novel GEFs (Levine et al, 2013b;De Franceschi et al, 2014;Daste et al, 2015).…”