5j45

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Crystal structure of Shrub, fly ortholog of SNF7/CHMP4B

Structural highlights

5j45 is a 1 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:X-ray diffraction, Resolution 2.758Å
Ligands:MSE
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CHM4_DROME Probable core polymerisation component of the endosomal sorting required for transport (ESCRT) III complex involved in multiple cellular processes requiring the outward bending of membranes, including vesicle budding, membrane repair and cytokinesis (Probable). The ESCRT pathway involves 4 complexes (ESCRT-0, -I, -II and -III) that sequentially assemble on the cytoplasmic side of membranes and induce membrane remodeling, budding and scission. As part of the ESCRT-III complex, involved in the budding of intraluminal vesicles (ILVs) into endosomes to form multivesicular bodies (MVBs), which target their contents for degradation via the endolysosomal pathway (PubMed:16713958). Involved in regulation of signal transduction pathways, including the Notch and BMP/decapentaplegic (dpp) pathways, by sequestering the intracellular domains of activated receptors into ILVs, isolating them from the cytoplasm and targeting them for lysosomal degradation (PubMed:22162134, PubMed:25804739). Involved in targeting ubiquitilated proteins, such as mono-ubiquitilanated N/Notch, to MVBs for degradation (PubMed:22162134, PubMed:33660341). Plays a role in wing development by regulating Notch signaling (PubMed:22162134). Involved in abscission of germline cells during oogenesis (PubMed:25647097). Involved in spermiogenesis (PubMed:33660341). Required for efficient cytoplasmic isolation and abscission during cytokinesis of epithelial sensory organ precursor cells (PubMed:37226981). May be involved in septate junction remodeling and maintenance (PubMed:37226981).[1] [2] [3] [4] [5] [6] [7]

Publication Abstract from PubMed

The endosomal sorting complex required for transport (ESCRT) is a conserved protein complex that facilitates budding and fission of membranes. It executes a key step in many cellular events, including cytokinesis and multi-vesicular body formation. The ESCRT-III protein Shrub in flies, or its homologs in yeast (Snf7) or humans (CHMP4B), is a critical polymerizing component of ESCRT-III needed to effect membrane fission. We report the structural basis for polymerization of Shrub and define a minimal region required for filament formation. The X-ray structure of the Shrub core shows that individual monomers in the lattice interact in a staggered arrangement using complementary electrostatic surfaces. Mutations that disrupt interface salt bridges interfere with Shrub polymerization and function. Despite substantial sequence divergence and differences in packing interactions, the arrangement of Shrub subunits in the polymer resembles that of Snf7 and other family homologs, suggesting that this intermolecular packing mechanism is shared among ESCRT-III proteins.

Electrostatic Interactions between Elongated Monomers Drive Filamentation of Drosophila Shrub, a Metazoan ESCRT-III Protein.,McMillan BJ, Tibbe C, Jeon H, Drabek AA, Klein T, Blacklow SC Cell Rep. 2016 Aug 2;16(5):1211-7. doi: 10.1016/j.celrep.2016.06.093. Epub 2016, Jul 21. PMID:27452459[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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References

  1. ↑ Sweeney NT, Brenman JE, Jan YN, Gao FB. The coiled-coil protein shrub controls neuronal morphogenesis in Drosophila. Curr Biol. 2006 May 23;16(10):1006-11. PMID:16713958 doi:10.1016/j.cub.2006.03.067
  2. ↑ Hori K, Sen A, Kirchhausen T, Artavanis-Tsakonas S. Synergy between the ESCRT-III complex and Deltex defines a ligand-independent Notch signal. J Cell Biol. 2011 Dec 12;195(6):1005-15. PMID:22162134 doi:10.1083/jcb.201104146
  3. ↑ Matias NR, Mathieu J, Huynh JR. Abscission is regulated by the ESCRT-III protein shrub in Drosophila germline stem cells. PLoS Genet. 2015 Feb 3;11(2):e1004653. PMID:25647097 doi:10.1371/journal.pgen.1004653
  4. ↑ Morawa KS, Schneider M, Klein T. Lgd regulates the activity of the BMP/Dpp signalling pathway during Drosophila oogenesis. Development. 2015 Apr 1;142(7):1325-35. PMID:25804739 doi:10.1242/dev.112961
  5. ↑ Chen MY, Tayyeb A, Wang YF. shrub is required for spermatogenesis of Drosophila melanogaster. Arch Insect Biochem Physiol. 2021 Apr;106(4):e21779. PMID:33660341 doi:10.1002/arch.21779
  6. ↑ Bruelle C, Pinot M, Daniel E, Daudé M, Mathieu J, Le Borgne R. Cell-intrinsic and -extrinsic roles of the ESCRT-III subunit Shrub in abscission of Drosophila sensory organ precursors. Development. 2023 May 15;150(10):dev201409. PMID:37226981 doi:10.1242/dev.201409
  7. ↑ Hori K, Sen A, Kirchhausen T, Artavanis-Tsakonas S. Synergy between the ESCRT-III complex and Deltex defines a ligand-independent Notch signal. J Cell Biol. 2011 Dec 12;195(6):1005-15. PMID:22162134 doi:10.1083/jcb.201104146
  8. ↑ McMillan BJ, Tibbe C, Jeon H, Drabek AA, Klein T, Blacklow SC. Electrostatic Interactions between Elongated Monomers Drive Filamentation of Drosophila Shrub, a Metazoan ESCRT-III Protein. Cell Rep. 2016 Aug 2;16(5):1211-7. doi: 10.1016/j.celrep.2016.06.093. Epub 2016, Jul 21. PMID:27452459 doi:http://dx.doi.org/10.1016/j.celrep.2016.06.093

Contents


PDB ID 5j45

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