7zcg

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CHMP2A-CHMP3 heterodimer (430 Angstrom diameter)

Structural highlights

7zcg is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.3Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CHM2A_HUMAN Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis (PubMed:21310966). Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). Recruited to the reforming nuclear envelope (NE) during anaphase by LEMD2 (PubMed:28242692). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4.[1] [2] [3] (Microbial infection) The ESCRT machinery functions in topologically equivalent membrane fission events, such as the budding of enveloped viruses (HIV-1 and other lentiviruses). Involved in HIV-1 p6- and p9-dependent virus release.[4] [5]

Publication Abstract from PubMed

The endosomal sorting complex required for transport (ESCRT) is a highly conserved protein machinery that drives a divers set of physiological and pathological membrane remodeling processes. However, the structural basis of ESCRT-III polymers stabilizing, constricting and cleaving negatively curved membranes is yet unknown. Here we present cryo-EM structures of membrane-coated CHMP2A-CHMP3 filaments from Homo sapiens of two different diameters at 3.3 and 3.6 A resolution. The structures reveal helical filaments assembled by CHMP2A-CHMP3 heterodimers in the open ESCRT-III conformation, which generates a partially positive charged membrane interaction surface, positions short N-terminal motifs for membrane interaction and the C-terminal VPS4 target sequence toward the tube interior. Inter-filament interactions are electrostatic, which may facilitate filament sliding upon VPS4-mediated polymer remodeling. Fluorescence microscopy as well as high-speed atomic force microscopy imaging corroborate that VPS4 can constrict and cleave CHMP2A-CHMP3 membrane tubes. We therefore conclude that CHMP2A-CHMP3-VPS4 act as a minimal membrane fission machinery.

Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly and membrane cleavage.,Azad K, Guilligay D, Boscheron C, Maity S, De Franceschi N, Sulbaran G, Effantin G, Wang H, Kleman JP, Bassereau P, Schoehn G, Roos WH, Desfosses A, Weissenhorn W Nat Struct Mol Biol. 2023 Jan;30(1):81-90. doi: 10.1038/s41594-022-00867-8. Epub , 2023 Jan 5. PMID:36604498[6]

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

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Citations
1 reviews cite this structure
Roles of ESCRT-III polymers in cell division across the tree of life.
Carlton et al. (2023)
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10 other articles
No citations found

See Also

References

  1. ↑ Guizetti J, Schermelleh L, Mantler J, Maar S, Poser I, Leonhardt H, Muller-Reichert T, Gerlich DW. Cortical constriction during abscission involves helices of ESCRT-III-dependent filaments. Science. 2011 Mar 25;331(6024):1616-20. doi: 10.1126/science.1201847. Epub 2011 , Feb 10. PMID:21310966 doi:http://dx.doi.org/10.1126/science.1201847
  2. ↑ Vietri M, Schink KO, Campsteijn C, Wegner CS, Schultz SW, Christ L, Thoresen SB, Brech A, Raiborg C, Stenmark H. Spastin and ESCRT-III coordinate mitotic spindle disassembly and nuclear envelope sealing. Nature. 2015 Jun 11;522(7555):231-5. doi: 10.1038/nature14408. Epub 2015 Jun 3. PMID:26040712 doi:http://dx.doi.org/10.1038/nature14408
  3. ↑ Gu M, LaJoie D, Chen OS, von Appen A, Ladinsky MS, Redd MJ, Nikolova L, Bjorkman PJ, Sundquist WI, Ullman KS, Frost A. LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope closure in fission yeast and human cells. Proc Natl Acad Sci U S A. 2017 Mar 14;114(11):E2166-E2175. doi: , 10.1073/pnas.1613916114. Epub 2017 Feb 27. PMID:28242692 doi:http://dx.doi.org/10.1073/pnas.1613916114
  4. ↑ von Schwedler UK, Stuchell M, Muller B, Ward DM, Chung HY, Morita E, Wang HE, Davis T, He GP, Cimbora DM, Scott A, Krausslich HG, Kaplan J, Morham SG, Sundquist WI. The protein network of HIV budding. Cell. 2003 Sep 19;114(6):701-13. PMID:14505570
  5. ↑ Martin-Serrano J, Yarovoy A, Perez-Caballero D, Bieniasz PD. Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins. Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12414-9. Epub 2003 Sep 30. PMID:14519844 doi:10.1073/pnas.2133846100
  6. ↑ Azad K, Guilligay D, Boscheron C, Maity S, De Franceschi N, Sulbaran G, Effantin G, Wang H, Kleman JP, Bassereau P, Schoehn G, Roos WH, Desfosses A, Weissenhorn W. Structural basis of CHMP2A-CHMP3 ESCRT-III polymer assembly and membrane cleavage. Nat Struct Mol Biol. 2023 Jan 5. doi: 10.1038/s41594-022-00867-8. PMID:36604498 doi:http://dx.doi.org/10.1038/s41594-022-00867-8

Contents


PDB ID 7zcg

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