5j45
Crystal structure of Shrub, fly ortholog of SNF7/CHMP4B
Structural highlights
FunctionCHM4_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 PubMedThe 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. References
| ||||||||||||||||||||
