| Structural highlights
Function
[GID4_YEAST] Substrate-recognition component of the GID complex, a multisubunit ubiquitin ligase that targets enzymes involved in gluconeogenesis for proteasomal degradation when cells are shifted to glucose-containing medium (PubMed:12686616, PubMed:18508925, PubMed:28126757). Specific for substrates with an N-terminal Pro (Pro/N-degron), including FBP1, ICL1 and MDH2 (PubMed:28126757). Has high affinity for the N-terminal sequence Pro-Thr-Leu-Val, and can bind peptides with an N-terminal sequence of the type Pro-[Gly,Ala,Ser,Thr,Asp,Asn,Tyr,His]-[Ala,Val,Leu,Ile,Lys,Arg]-[Val,Cys,Pro,Leu,Ile,Trp] (PubMed:28126757). Required for vacuolar degradation of FBP1 when cells are shifted to glucose-containing medium, probably by targeting FBP1-containing vesicles to the vacuole, but is not required for FBP1 sequestration in cytoplasmic vesicles (PubMed:9508768).[1] [2] [3] [4] [VID28_YEAST] Required for the adaptation to the presence of glucose in the growth medium; mediates the degradation of enzymes involved in gluconeogenesis when cells are shifted to glucose-containing medium (PubMed:12686616). Required for proteasome-dependent catabolite degradation of fructose-1,6-bisphosphatase (FBP1) (PubMed:12686616).[5] [VID30_YEAST] Required for the adaptation to the presence of glucose in the growth medium; mediates the degradation of enzymes involved in gluconeogenesis when cells are shifted to glucose-containing medium (PubMed:9737955, PubMed:12686616). Required for proteasome-dependent catabolite degradation of fructose-1,6-bisphosphatase (FBP1) (PubMed:9737955, PubMed:12686616, PubMed:22645139, PubMed:28126757).[6] [7] [8] [9] [GID8_YEAST] Required for the adaptation to the presence of glucose in the growth medium; mediates the degradation of enzymes involved in gluconeogenesis when cells are shifted to glucose-containing medium (PubMed:12686616). Required for proteasome-dependent catabolite degradation of fructose-1,6-bisphosphatase (FBP1) (PubMed:12686616). Required also for cell cycle progression. Positively controls G1 and the timing of START (PubMed:15590836).[10] [11] [FYV10_YEAST] Required for the adaptation to the presence of glucose in the growth medium; mediates the degradation of enzymes involved in gluconeogenesis when cells are shifted to glucose-containing medium (PubMed:12686616, PubMed:22044534). Required for proteasome-dependent catabolite degradation of fructose-1,6-bisphosphatase (FBP1) (PubMed:12686616, PubMed:22044534). May catalyze ubiquitination of target proteins in complex with RMD5 (Probable). Required for survival upon exposure to K1 killer toxin (PubMed:12663529).[12] [13] [14]
Publication Abstract from PubMed
Cells respond to environmental changes by toggling metabolic pathways, preparing for homeostasis, and anticipating future stresses. For example, in Saccharomyces cerevisiae, carbon stress-induced gluconeogenesis is terminated upon glucose availability, a process that involves the multiprotein E3 ligase GID(SR4) recruiting N termini and catalyzing ubiquitylation of gluconeogenic enzymes. Here, genetics, biochemistry, and cryoelectron microscopy define molecular underpinnings of glucose-induced degradation. Unexpectedly, carbon stress induces an inactive anticipatory complex (GID(Ant)), which awaits a glucose-induced substrate receptor to form the active GID(SR4). Meanwhile, other environmental perturbations elicit production of an alternative substrate receptor assembling into a related E3 ligase complex. The intricate structure of GID(Ant) enables anticipating and ultimately binding various N-degron-targeting (i.e., "N-end rule") substrate receptors, while the GID(SR4) E3 forms a clamp-like structure juxtaposing substrate lysines with the ubiquitylation active site. The data reveal evolutionarily conserved GID complexes as a family of multisubunit E3 ubiquitin ligases responsive to extracellular stimuli.
Interconversion between Anticipatory and Active GID E3 Ubiquitin Ligase Conformations via Metabolically Driven Substrate Receptor Assembly.,Qiao S, Langlois CR, Chrustowicz J, Sherpa D, Karayel O, Hansen FM, Beier V, von Gronau S, Bollschweiler D, Schafer T, Alpi AF, Mann M, Prabu JR, Schulman BA Mol Cell. 2019 Nov 1. pii: S1097-2765(19)30769-5. doi:, 10.1016/j.molcel.2019.10.009. PMID:31708416[15]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Regelmann J, Schule T, Josupeit FS, Horak J, Rose M, Entian KD, Thumm M, Wolf DH. Catabolite degradation of fructose-1,6-bisphosphatase in the yeast Saccharomyces cerevisiae: a genome-wide screen identifies eight novel GID genes and indicates the existence of two degradation pathways. Mol Biol Cell. 2003 Apr;14(4):1652-63. doi: 10.1091/mbc.e02-08-0456. PMID:12686616 doi:http://dx.doi.org/10.1091/mbc.e02-08-0456
- ↑ Santt O, Pfirrmann T, Braun B, Juretschke J, Kimmig P, Scheel H, Hofmann K, Thumm M, Wolf DH. The yeast GID complex, a novel ubiquitin ligase (E3) involved in the regulation of carbohydrate metabolism. Mol Biol Cell. 2008 Aug;19(8):3323-33. doi: 10.1091/mbc.e08-03-0328. Epub 2008, May 28. PMID:18508925 doi:http://dx.doi.org/10.1091/mbc.e08-03-0328
- ↑ Chen SJ, Wu X, Wadas B, Oh JH, Varshavsky A. An N-end rule pathway that recognizes proline and destroys gluconeogenic enzymes. Science. 2017 Jan 27;355(6323). pii: 355/6323/eaal3655. doi:, 10.1126/science.aal3655. PMID:28126757 doi:http://dx.doi.org/10.1126/science.aal3655
- ↑ Chiang MC, Chiang HL. Vid24p, a novel protein localized to the fructose-1, 6-bisphosphatase-containing vesicles, regulates targeting of fructose-1,6-bisphosphatase from the vesicles to the vacuole for degradation. J Cell Biol. 1998 Mar 23;140(6):1347-56. doi: 10.1083/jcb.140.6.1347. PMID:9508768 doi:http://dx.doi.org/10.1083/jcb.140.6.1347
- ↑ Regelmann J, Schule T, Josupeit FS, Horak J, Rose M, Entian KD, Thumm M, Wolf DH. Catabolite degradation of fructose-1,6-bisphosphatase in the yeast Saccharomyces cerevisiae: a genome-wide screen identifies eight novel GID genes and indicates the existence of two degradation pathways. Mol Biol Cell. 2003 Apr;14(4):1652-63. doi: 10.1091/mbc.e02-08-0456. PMID:12686616 doi:http://dx.doi.org/10.1091/mbc.e02-08-0456
- ↑ Regelmann J, Schule T, Josupeit FS, Horak J, Rose M, Entian KD, Thumm M, Wolf DH. Catabolite degradation of fructose-1,6-bisphosphatase in the yeast Saccharomyces cerevisiae: a genome-wide screen identifies eight novel GID genes and indicates the existence of two degradation pathways. Mol Biol Cell. 2003 Apr;14(4):1652-63. doi: 10.1091/mbc.e02-08-0456. PMID:12686616 doi:http://dx.doi.org/10.1091/mbc.e02-08-0456
- ↑ Menssen R, Schweiggert J, Schreiner J, Kusevic D, Reuther J, Braun B, Wolf DH. Exploring the topology of the Gid complex, the E3 ubiquitin ligase involved in catabolite-induced degradation of gluconeogenic enzymes. J Biol Chem. 2012 Jul 20;287(30):25602-14. doi: 10.1074/jbc.M112.363762. Epub, 2012 May 29. PMID:22645139 doi:http://dx.doi.org/10.1074/jbc.M112.363762
- ↑ Chen SJ, Wu X, Wadas B, Oh JH, Varshavsky A. An N-end rule pathway that recognizes proline and destroys gluconeogenic enzymes. Science. 2017 Jan 27;355(6323). pii: 355/6323/eaal3655. doi:, 10.1126/science.aal3655. PMID:28126757 doi:http://dx.doi.org/10.1126/science.aal3655
- ↑ Hammerle M, Bauer J, Rose M, Szallies A, Thumm M, Dusterhus S, Mecke D, Entian KD, Wolf DH. Proteins of newly isolated mutants and the amino-terminal proline are essential for ubiquitin-proteasome-catalyzed catabolite degradation of fructose-1,6-bisphosphatase of Saccharomyces cerevisiae. J Biol Chem. 1998 Sep 25;273(39):25000-5. doi: 10.1074/jbc.273.39.25000. PMID:9737955 doi:http://dx.doi.org/10.1074/jbc.273.39.25000
- ↑ Regelmann J, Schule T, Josupeit FS, Horak J, Rose M, Entian KD, Thumm M, Wolf DH. Catabolite degradation of fructose-1,6-bisphosphatase in the yeast Saccharomyces cerevisiae: a genome-wide screen identifies eight novel GID genes and indicates the existence of two degradation pathways. Mol Biol Cell. 2003 Apr;14(4):1652-63. doi: 10.1091/mbc.e02-08-0456. PMID:12686616 doi:http://dx.doi.org/10.1091/mbc.e02-08-0456
- ↑ Pathak R, Bogomolnaya LM, Guo J, Polymenis M. Gid8p (Dcr1p) and Dcr2p function in a common pathway to promote START completion in Saccharomyces cerevisiae. Eukaryot Cell. 2004 Dec;3(6):1627-38. PMID:15590836 doi:http://dx.doi.org/3/6/1627
- ↑ Page N, Gerard-Vincent M, Menard P, Beaulieu M, Azuma M, Dijkgraaf GJ, Li H, Marcoux J, Nguyen T, Dowse T, Sdicu AM, Bussey H. A Saccharomyces cerevisiae genome-wide mutant screen for altered sensitivity to K1 killer toxin. Genetics. 2003 Mar;163(3):875-94. PMID:12663529
- ↑ Regelmann J, Schule T, Josupeit FS, Horak J, Rose M, Entian KD, Thumm M, Wolf DH. Catabolite degradation of fructose-1,6-bisphosphatase in the yeast Saccharomyces cerevisiae: a genome-wide screen identifies eight novel GID genes and indicates the existence of two degradation pathways. Mol Biol Cell. 2003 Apr;14(4):1652-63. doi: 10.1091/mbc.e02-08-0456. PMID:12686616 doi:http://dx.doi.org/10.1091/mbc.e02-08-0456
- ↑ Braun B, Pfirrmann T, Menssen R, Hofmann K, Scheel H, Wolf DH. Gid9, a second RING finger protein contributes to the ubiquitin ligase activity of the Gid complex required for catabolite degradation. FEBS Lett. 2011 Dec 15;585(24):3856-61. doi: 10.1016/j.febslet.2011.10.038. Epub , 2011 Oct 29. PMID:22044534 doi:http://dx.doi.org/10.1016/j.febslet.2011.10.038
- ↑ Qiao S, Langlois CR, Chrustowicz J, Sherpa D, Karayel O, Hansen FM, Beier V, von Gronau S, Bollschweiler D, Schafer T, Alpi AF, Mann M, Prabu JR, Schulman BA. Interconversion between Anticipatory and Active GID E3 Ubiquitin Ligase Conformations via Metabolically Driven Substrate Receptor Assembly. Mol Cell. 2019 Nov 1. pii: S1097-2765(19)30769-5. doi:, 10.1016/j.molcel.2019.10.009. PMID:31708416 doi:http://dx.doi.org/10.1016/j.molcel.2019.10.009
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