6vps

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Cryo-EM structure of the amyloid core of Drosophila Orb2 isolated from headCryo-EM structure of the amyloid core of Drosophila Orb2 isolated from head

Structural highlights

6vps is a 9 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 2.6Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ORB2_DROME Required in mushroom body gamma neurons for long-term memory in male courtship (PubMed:17965711, PubMed:23083740). Binds to mRNA 3'-UTRs (PubMed:20547833, PubMed:26638074, PubMed:24830287, PubMed:26095367). In its monomeric form, acts as a translational repressor of genes involved in neuronal growth, synapse formation and protein turnover (PubMed:20547833, PubMed:26638074). In its amyloid-like oligomeric form, acts as a translational activator (PubMed:26638074). The monomeric form reduces poly(A) tail length and destabilizes mRNA while the oligomeric form protects and elongates the poly(A) tail and stabilizes mRNA (PubMed:26638074). Isoform A is required for initial memory acquisition and, following subsequent late dopaminergic pathway activation, isoform A recruits isoform B into a complex to activate translation of CaMKII which is required for long-term memory consolidation (PubMed:26095367). Involved in asymmetric cell division in the central nervous system (PubMed:21900268). Required for the progression of spermatogenesis through meiosis and for sperm differentiation (PubMed:23209437). During sperm differentiation, required to asymmetrically localize and activate the translation of protein kinase aPKC mRNAs which is necessary for spermatid cyst polarization (PubMed:24830287). Also required during spermatid cyst polarization for localization and translation of its own mRNA (PubMed:24830287).[1] [2] [3] [4] [5] [6] [7] [8]

References

  1. Keleman K, Kruttner S, Alenius M, Dickson BJ. Function of the Drosophila CPEB protein Orb2 in long-term courtship memory. Nat Neurosci. 2007 Dec;10(12):1587-93. doi: 10.1038/nn1996. Epub 2007 Oct 28. PMID:17965711 doi:http://dx.doi.org/10.1038/nn1996
  2. Mastushita-Sakai T, White-Grindley E, Samuelson J, Seidel C, Si K. Drosophila Orb2 targets genes involved in neuronal growth, synapse formation, and protein turnover. Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11987-92. doi:, 10.1073/pnas.1004433107. Epub 2010 Jun 14. PMID:20547833 doi:http://dx.doi.org/10.1073/pnas.1004433107
  3. Hafer N, Xu S, Bhat KM, Schedl P. The Drosophila CPEB protein Orb2 has a novel expression pattern and is important for asymmetric cell division and nervous system function. Genetics. 2011 Nov;189(3):907-21. doi: 10.1534/genetics.110.123646. Epub 2011 Sep, 6. PMID:21900268 doi:http://dx.doi.org/10.1534/genetics.110.123646
  4. Kruttner S, Stepien B, Noordermeer JN, Mommaas MA, Mechtler K, Dickson BJ, Keleman K. Drosophila CPEB Orb2A mediates memory independent of Its RNA-binding domain. Neuron. 2012 Oct 18;76(2):383-95. doi: 10.1016/j.neuron.2012.08.028. Epub 2012, Oct 17. PMID:23083740 doi:http://dx.doi.org/10.1016/j.neuron.2012.08.028
  5. Xu S, Hafer N, Agunwamba B, Schedl P. The CPEB protein Orb2 has multiple functions during spermatogenesis in Drosophila melanogaster. PLoS Genet. 2012;8(11):e1003079. doi: 10.1371/journal.pgen.1003079. Epub 2012 Nov, 29. PMID:23209437 doi:http://dx.doi.org/10.1371/journal.pgen.1003079
  6. Xu S, Tyagi S, Schedl P. Spermatid cyst polarization in Drosophila depends upon apkc and the CPEB family translational regulator orb2. PLoS Genet. 2014 May 15;10(5):e1004380. doi: 10.1371/journal.pgen.1004380., eCollection 2014 May. PMID:24830287 doi:http://dx.doi.org/10.1371/journal.pgen.1004380
  7. Kruttner S, Traunmuller L, Dag U, Jandrasits K, Stepien B, Iyer N, Fradkin LG, Noordermeer JN, Mensh BD, Keleman K. Synaptic Orb2A Bridges Memory Acquisition and Late Memory Consolidation in Drosophila. Cell Rep. 2015 Jun 30;11(12):1953-65. doi: 10.1016/j.celrep.2015.05.037. Epub, 2015 Jun 18. PMID:26095367 doi:http://dx.doi.org/10.1016/j.celrep.2015.05.037
  8. Khan MR, Li L, Perez-Sanchez C, Saraf A, Florens L, Slaughter BD, Unruh JR, Si K. Amyloidogenic Oligomerization Transforms Drosophila Orb2 from a Translation Repressor to an Activator. Cell. 2015 Dec 3;163(6):1468-83. doi: 10.1016/j.cell.2015.11.020. PMID:26638074 doi:http://dx.doi.org/10.1016/j.cell.2015.11.020

6vps, resolution 2.60Å

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