2zme

From Proteopedia

Integrated structural and functional model of the human ESCRT-II complex

Structural highlights

2zme is a 4 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:	X-ray diffraction, Resolution 2.9Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SNF8_HUMAN Component of the endosomal sorting complex required for transport II (ESCRT-II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. The ESCRT-II complex may also play a role in transcription regulation by participating in derepression of transcription by RNA polymerase II, possibly via its interaction with ELL. Required for degradation of both endocytosed EGF and EGFR, but not for the EGFR ligand-mediated internalization. It is also required for the degradation of CXCR4.^[1] ^[2] ^[3]

Evolutionary Conservation

Checkto colour the structure by Evolutionary Conservation, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

ESCRT-II plays a pivotal role in receptor downregulation and multivesicular body biogenesis and is conserved from yeast to humans. The crystal structures of two human ESCRT-II complex structures have been determined at 2.6 and 2.9 A resolution, respectively. The complex has three lobes and contains one copy each of VPS22 and VPS36 and two copies of VPS25. The structure reveals a dynamic helical domain to which both the VPS22 and VPS36 subunits contribute that connects the GLUE domain to the rest of the ESCRT-II core. Hydrodynamic analysis shows that intact ESCRT-II has a compact, closed conformation. ESCRT-II binds to the ESCRT-I VPS28 C-terminal domain subunit through a helix immediately C-terminal to the VPS36-GLUE domain. ESCRT-II is targeted to endosomal membranes by the lipid-binding activities of both the Vps36 GLUE domain and the first helix of Vps22. These data provide a unifying structural and functional framework for the ESCRT-II complex.

Integrated structural model and membrane targeting mechanism of the human ESCRT-II complex.,Im YJ, Hurley JH Dev Cell. 2008 Jun;14(6):902-13. PMID:18539118^[4]

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

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Citations

reviews cite this structure

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References

↑ Progida C, Malerod L, Stuffers S, Brech A, Bucci C, Stenmark H. RILP is required for the proper morphology and function of late endosomes. J Cell Sci. 2007 Nov 1;120(Pt 21):3729-37. PMID:17959629 doi:http://dx.doi.org/10.1242/jcs.017301
↑ Malerod L, Stuffers S, Brech A, Stenmark H. Vps22/EAP30 in ESCRT-II mediates endosomal sorting of growth factor and chemokine receptors destined for lysosomal degradation. Traffic. 2007 Nov;8(11):1617-29. Epub 2007 Aug 20. PMID:17714434 doi:http://dx.doi.org/10.1111/j.1600-0854.2007.00630.x
↑ Raiborg C, Malerod L, Pedersen NM, Stenmark H. Differential functions of Hrs and ESCRT proteins in endocytic membrane trafficking. Exp Cell Res. 2008 Feb 15;314(4):801-13. Epub 2007 Nov 26. PMID:18031739 doi:http://dx.doi.org/10.1016/j.yexcr.2007.10.014
↑ Im YJ, Hurley JH. Integrated structural model and membrane targeting mechanism of the human ESCRT-II complex. Dev Cell. 2008 Jun;14(6):902-13. PMID:18539118 doi:10.1016/j.devcel.2008.04.004