View source for 7zcg


==CHMP2A-CHMP3 heterodimer (430 Angstrom diameter)==
<StructureSection load='7zcg' size='340' side='right'caption='[[7zcg]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7zcg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZCG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZCG FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7zcg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zcg OCA], [https://pdbe.org/7zcg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zcg RCSB], [https://www.ebi.ac.uk/pdbsum/7zcg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zcg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CHM2A_HUMAN 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.<ref>PMID:21310966</ref> <ref>PMID:26040712</ref> <ref>PMID:28242692</ref>   (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.<ref>PMID:14505570</ref> <ref>PMID:14519844</ref> 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:36604498</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7zcg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Vacuolar protein sorting-associated protein 3D structures|Vacuolar protein sorting-associated protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Azad K]]
[[Category: Desfosses A]]
[[Category: Effantin G]]
[[Category: Schoehn G]]
[[Category: Weissenhorn W]]