Intramolecular protein-protein and protein-lipid interactions control the conformation and subcellular targeting of neuronal Ykt6

Abstract

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Structure and function of longin SNAREs

“…As mentioned above, unlike the two other longin SNAREs, Ykt6 does not contain a transmembrane domain that anchors it permanently to membranes, but instead, the protein uses a lipid anchor that allows transient association with the membrane (Fukasawa et al, 2004); thus, Ykt6 can easily insert into potentially affected compartments -for example, ER membranes that have accumulated a toxic amount of proteins in the case of Parkinson's disease -to rescue transport. The longin domain of Ykt6 has been found to be necessary and sufficient both for targeting Ykt6 to the secretory pathway and for its role in particle formation (Fukasawa et al, 2004;Hasegawa et al, 2004). The molecular mechanisms underlying the aggregation of the soluble pool of Ykt6 are still poorly understood, in contrast to the membrane-anchoring mechanism, which has been fully elucidated and is tightly linked to the conformational transition of Ykt6 from a closed (inactive) to an open (active) state (Fukasawa Rab GTPase exchange factors…”

Identification of the Yeast R-SNARE Nyv1p as a Novel Longin Domain-containing Protein

“…minus of the protein (Hasegawa et al, 2004). In contrast, the longin domain of Sec22b does not contain such a hydrophobic surface, and the SNARE-motif of Sec22b does not bind to the longin domain but rather adopts an open conformation (Gonzalez et al, 2001).…”

“…These include subunits of the adaptin complexes (Collins et al, 2002;Heldwein et al, 2004) and SEDL/Trs20p (Jang et al, 2002), a common subunit of the transport protein particle (TRAPP)I and TRAPPII multisubunit complexes, which are required for traffic between the ER and Golgi and within the Golgi (Oka and Krieger, 2005). The function of the longin fold of Sec22b/Sec22p is unknown, but in Ykt6p the longin domain folds back and binds to the SNARE-motif of the protein (Tochio et al, 2001), and this conformation is likely to be important for chaperoning the lipid modified C terminus of the cytoplasmic form of Ykt6p in cells as well as for its localization (Fukasawa et al, 2004;Hasegawa et al, 2004).…”

Yeast vacuole fusion: A model system for eukaryotic endomembrane dynamics

“…On membranes, Ykt6 is both prenylated and palmitoylated, whereas it is believed to be depalmitoylated upon dissociation from membranes. [110][111][112] In its cytosolic state, the N-terminal longin-domain of Ykt6 is thought to fold back onto its C-terminal coiled-coil domain, thereby enveloping its hydrophobic prenyl anchor. 113 Ykt6 may regulate its own palmitoylation and depalmitoylation 114 and thereby determine its localization.…”

“…113 Ykt6 may regulate its own palmitoylation and depalmitoylation 114 and thereby determine its localization. 110,111 The function of Ykt6 at the vacuole remains puzzling. It is implicated to function in several trafficking pathways towards the vacuole, i.e.…”