Structural highlights
Function
[TLG1_YEAST] SNARE protein (of Qc type) involved in membrane fusion probably in retrograde traffic of cytosolic double-membrane vesicles derived from both, early and possibly late endosomes/PVC (prevacuolar compartment) back to the trans-Golgi network (TGN or late Golgi). It has been reported to function both as a (target membrane) t-SNARE and as a (vesicle) v-SNARE. Upon vesicle tethering to the target membrane, which requires additional proteins, a SNARE-pin is formed. This is a very stable 4 parallel alpha-helical coil bundle consisting of 4 SNARE domains (usually one of each type: Qa, Qb, Qc, and R), of which at least one is anchored in the opposite membrane. The formation of the SNARE-pin is believed to bring the two membranes in close proximity and to provide the energy to drive membrane fusion. Through its interaction with the VFT (or GARP) complex, it may also contribute to vesicle recognition specificity and tethering. Regulation of SNARE-pin formation also seems to depend on the phosphorylation state of the protein, phosphorylation by TPK1 causing inhibition and dephosphorylation by SIT4 activation.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
Membrane fusion in cells involves the interaction of SNARE proteins on apposing membranes. Formation of SNARE complexes is preceded by tethering events, and a number of protein complexes that are thought to mediate this have been identified. The VFT or GARP complex is required for endosome-Golgi traffic in yeast. It consists of four subunits, one of which, Vps51, has been shown to bind specifically to the SNARE Tlg1, which participates in the same fusion event. We have determined the structure of the N-terminal domain of Tlg1 bound to a peptide from the N terminus of Vps51. Binding depends mainly on residues 18-30 of Vps51. These form a short helix which lies in a conserved groove in the three-helix bundle formed by Tlg1. Surprisingly, although both Vps51 and Tlg1 are required for transport to the late Golgi from endosomes, removal of the Tlg1-binding sequences from Vps51 does not block such traffic in vivo. Thus, this particular interaction cannot be crucial to the process of vesicle docking or fusion.
Structural analysis of the interaction between the SNARE Tlg1 and Vps51.,Fridmann-Sirkis Y, Kent HM, Lewis MJ, Evans PR, Pelham HR Traffic. 2006 Feb;7(2):182-90. PMID:16420526[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Holthuis JC, Nichols BJ, Dhruvakumar S, Pelham HR. Two syntaxin homologues in the TGN/endosomal system of yeast. EMBO J. 1998 Jan 2;17(1):113-26. PMID:9427746 doi:http://dx.doi.org/10.1093/emboj/17.1.113
- ↑ Coe JG, Lim AC, Xu J, Hong W. A role for Tlg1p in the transport of proteins within the Golgi apparatus of Saccharomyces cerevisiae. Mol Biol Cell. 1999 Jul;10(7):2407-23. PMID:10397773
- ↑ Siniossoglou S, Pelham HR. An effector of Ypt6p binds the SNARE Tlg1p and mediates selective fusion of vesicles with late Golgi membranes. EMBO J. 2001 Nov 1;20(21):5991-8. PMID:11689439 doi:10.1093/emboj/20.21.5991
- ↑ Paumet F, Brugger B, Parlati F, McNew JA, Sollner TH, Rothman JE. A t-SNARE of the endocytic pathway must be activated for fusion. J Cell Biol. 2001 Dec 10;155(6):961-8. Epub 2001 Dec 10. PMID:11739407 doi:http://dx.doi.org/10.1083/jcb.200104092
- ↑ Siniossoglou S, Pelham HR. Vps51p links the VFT complex to the SNARE Tlg1p. J Biol Chem. 2002 Dec 13;277(50):48318-24. Epub 2002 Oct 10. PMID:12377769 doi:10.1074/jbc.M209428200
- ↑ Conibear E, Cleck JN, Stevens TH. Vps51p mediates the association of the GARP (Vps52/53/54) complex with the late Golgi t-SNARE Tlg1p. Mol Biol Cell. 2003 Apr;14(4):1610-23. PMID:12686613 doi:10.1091/mbc.E02-10-0654
- ↑ Fridmann-Sirkis Y, Kent HM, Lewis MJ, Evans PR, Pelham HR. Structural analysis of the interaction between the SNARE Tlg1 and Vps51. Traffic. 2006 Feb;7(2):182-90. PMID:16420526 doi:TRA374
