| Structural highlights
Function
BET3_YEAST Component of the TRAPP I, TRAPP II and TRAPP III complexes which act as guanine nucleotide exchange factors (GEF) for YPT1. TRAPP I plays a key role in the late stages of endoplasmic reticulum to Golgi traffic. TRAPP II plays a role in intra-Golgi transport. TRAPP III plays a role in autophagosome formation. Required for sporulation. Has a role late in meiosis following DNA replication.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
The GTPase Rab1 is a master regulator of the early secretory pathway and is critical for autophagy. Rab1 activation is controlled by its guanine nucleotide exchange factor, the multisubunit TRAPPIII complex. Here, we report the 3.7 A cryo-EM structure of the Saccharomyces cerevisiae TRAPPIII complex bound to its substrate Rab1/Ypt1. The structure reveals the binding site for the Rab1/Ypt1 hypervariable domain, leading to a model for how the complex interacts with membranes during the activation reaction. We determined that stable membrane binding by the TRAPPIII complex is required for robust activation of Rab1/Ypt1 in vitro and in vivo, and is mediated by a conserved amphipathic alpha-helix within the regulatory Trs85 subunit. Our results show that the Trs85 subunit serves as a membrane anchor, via its amphipathic helix, for the entire TRAPPIII complex. These findings provide a structural understanding of Rab activation on organelle and vesicle membranes.
Structural basis of TRAPPIII-mediated Rab1 activation.,Joiner AM, Phillips BP, Yugandhar K, Sanford EJ, Smolka MB, Yu H, Miller EA, Fromme JC EMBO J. 2021 Jun 15;40(12):e107607. doi: 10.15252/embj.2020107607. Epub 2021 May , 21. PMID:34018207[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rossi G, Kolstad K, Stone S, Palluault F, Ferro-Novick S. BET3 encodes a novel hydrophilic protein that acts in conjunction with yeast SNAREs. Mol Biol Cell. 1995 Dec;6(12):1769-80. PMID:8590804
- ↑ Sacher M, Jiang Y, Barrowman J, Scarpa A, Burston J, Zhang L, Schieltz D, Yates JR 3rd, Abeliovich H, Ferro-Novick S. TRAPP, a highly conserved novel complex on the cis-Golgi that mediates vesicle docking and fusion. EMBO J. 1998 May 1;17(9):2494-503. PMID:9564032 doi:http://dx.doi.org/10.1093/emboj/17.9.2494
- ↑ Sacher M, Barrowman J, Wang W, Horecka J, Zhang Y, Pypaert M, Ferro-Novick S. TRAPP I implicated in the specificity of tethering in ER-to-Golgi transport. Mol Cell. 2001 Feb;7(2):433-42. PMID:11239471
- ↑ Yip CK, Berscheminski J, Walz T. Molecular architecture of the TRAPPII complex and implications for vesicle tethering. Nat Struct Mol Biol. 2010 Nov;17(11):1298-304. doi: 10.1038/nsmb.1914. Epub 2010 , Oct 24. PMID:20972447 doi:http://dx.doi.org/10.1038/nsmb.1914
- ↑ Lynch-Day MA, Bhandari D, Menon S, Huang J, Cai H, Bartholomew CR, Brumell JH, Ferro-Novick S, Klionsky DJ. Trs85 directs a Ypt1 GEF, TRAPPIII, to the phagophore to promote autophagy. Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7811-6. doi:, 10.1073/pnas.1000063107. Epub 2010 Apr 7. PMID:20375281 doi:http://dx.doi.org/10.1073/pnas.1000063107
- ↑ Joiner AM, Phillips BP, Yugandhar K, Sanford EJ, Smolka MB, Yu H, Miller EA, Fromme JC. Structural basis of TRAPPIII-mediated Rab1 activation. EMBO J. 2021 Jun 15;40(12):e107607. PMID:34018207 doi:10.15252/embj.2020107607
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