8pmq: Difference between revisions

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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/RMD5_YEAST RMD5_YEAST] E3 ubiquitin-protein ligase component of the GID complex (PubMed:12686616, PubMed:18508925). 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:18508925). Required for proteasome-dependent catabolite degradation of fructose-1,6-bisphosphatase (FBP1) (PubMed:9737955, PubMed:12686616, PubMed:18508925, PubMed:28126757).<ref>PMID:12686616</ref> <ref>PMID:18508925</ref> <ref>PMID:28126757</ref> <ref>PMID:9737955</ref>  
[https://www.uniprot.org/uniprot/RMD5_YEAST RMD5_YEAST] E3 ubiquitin-protein ligase component of the GID complex (PubMed:12686616, PubMed:18508925). 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:18508925). Required for proteasome-dependent catabolite degradation of fructose-1,6-bisphosphatase (FBP1) (PubMed:9737955, PubMed:12686616, PubMed:18508925, PubMed:28126757).<ref>PMID:12686616</ref> <ref>PMID:18508925</ref> <ref>PMID:28126757</ref> <ref>PMID:9737955</ref>  
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== Publication Abstract from PubMed ==
Ubiquitylation is catalyzed by coordinated actions of E3 and E2 enzymes. Molecular principles governing many important E3-E2 partnerships remain unknown, including those for RING-family GID/CTLH E3 ubiquitin ligases and their dedicated E2, Ubc8/UBE2H (yeast/human nomenclature). GID/CTLH-Ubc8/UBE2H-mediated ubiquitylation regulates biological processes ranging from yeast metabolic signaling to human development. Here, cryoelectron microscopy (cryo-EM), biochemistry, and cell biology reveal this exquisitely specific E3-E2 pairing through an unconventional catalytic assembly and auxiliary interactions 70-100 A away, mediated by E2 multisite phosphorylation. Rather than dynamic polyelectrostatic interactions reported for other ubiquitylation complexes, multiple Ubc8/UBE2H phosphorylation sites within acidic CK2-targeted sequences specifically anchor the E2 C termini to E3 basic patches. Positions of phospho-dependent interactions relative to the catalytic domains correlate across evolution. Overall, our data show that phosphorylation-dependent multivalency establishes a specific E3-E2 partnership, is antagonistic with dephosphorylation, rigidifies the catalytic centers within a flexing GID E3-substrate assembly, and facilitates substrate collision with ubiquitylation active sites.
Multisite phosphorylation dictates selective E2-E3 pairing as revealed by Ubc8/UBE2H-GID/CTLH assemblies.,Chrustowicz J, Sherpa D, Li J, Langlois CR, Papadopoulou EC, Vu DT, Hehl LA, Karayel O, Beier V, von Gronau S, Muller J, Prabu JR, Mann M, Kleiger G, Alpi AF, Schulman BA Mol Cell. 2023 Dec 8:S1097-2765(23)00972-3. doi: 10.1016/j.molcel.2023.11.027. PMID:38113892<ref>PMID:38113892</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
== References ==
<references/>
<references/>

Revision as of 13:59, 21 February 2024

Catalytic module of yeast GID E3 ligase bound to multiphosphorylated Ubc8~ubiquitinCatalytic module of yeast GID E3 ligase bound to multiphosphorylated Ubc8~ubiquitin

Structural highlights

8pmq is a 4 chain structure with sequence from Homo sapiens and Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.53Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RMD5_YEAST E3 ubiquitin-protein ligase component of the GID complex (PubMed:12686616, PubMed:18508925). 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:18508925). Required for proteasome-dependent catabolite degradation of fructose-1,6-bisphosphatase (FBP1) (PubMed:9737955, PubMed:12686616, PubMed:18508925, PubMed:28126757).[1] [2] [3] [4]

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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

8pmq, resolution 3.53Å

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