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| Subject Categories: Membranes & Transport | Structural Biology |
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| The EMBO Journal
(2007) 26, 600–612, doi:10.1038/sj.emboj.7601501 Published online 11 January 2007 |
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| Structural insight into the ESCRT-I/-II link and its role in MVB trafficking |
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| David J Gill1, Hsiangling Teo1, Ji Sun2, Olga Perisic1, Dmitry B Veprintsev3, Scott D Emr2 and Roger L Williams1 |
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1 MRC Laboratory of Molecular Biology, Medical Research Council Centre, Cambridge, UK 2 Department of Cellular and Molecular Medicine, The Howard Hughes Medical Institute, University of California, San Diego, School of Medicine, La Jolla, CA, USA 3 Centre for Protein Engineering, Medical Research Council Centre, Cambridge, UK To whom correspondence should be addressed David J Gill, Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Hills Road, Cambridge, Cambridgeshire CB2 2QH, UK. Tel.: +44 1223 402164; Fax: +44 1223 412178; E-mail: djg38@mrc-lmb.cam.ac.uk Received 22 August 2006; Accepted 20 November 2006; Published online 11 January 2007. |
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| Abstract |
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| ESCRT (endosomal sorting complex required for transport) complexes orchestrate efficient sorting of ubiquitinated transmembrane receptors to lysosomes via multivesicular bodies (MVBs). Yeast ESCRT-I and ESCRT-II interact directly in vitro; however, this association is not detected in yeast cytosol. To gain understanding of the molecular mechanisms of this link, we have characterised the ESCRT-I/-II supercomplex and determined the crystal structure of its interface. The link is formed by the vacuolar protein sorting (Vps)28 C-terminus (ESCRT-I) binding with nanomolar affinity to the Vps36-NZF-N zinc-finger domain (ESCRT-II). A hydrophobic patch on the Vps28-CT four-helix bundle contacts the hydrophobic knuckles of Vps36-NZF-N. Mutation of the ESCRT-I/-II link results in a cargo-sorting defect in yeast. Interestingly, the two Vps36 NZF domains, NZF-N and NZF-C, despite having the same core fold, use distinct surfaces to bind ESCRT-I or ubiquitinated cargo. We also show that a new component of ESCRT-I, Mvb12 (YGR206W), engages ESCRT-I directly with nanomolar affinity to form a 1:1:1:1 heterotetramer. Mvb12 does not affect the affinity of ESCRT-I for ESCRT-II in vitro. Our data suggest a complex regulatory mechanism for the ESCRT-I/-II link in yeast. |
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| Keywords: CHMP, ESCRT, HIV budding, MVB, NZF finger |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSStructural biology ESCRT service Nature News and Views (21 Jun 2007) Nature Structural & Molecular Biology News and Views (01 Apr 2007) RESEARCHStructural insight into the ESCRT-I/-II link and its role in MVB trafficking The EMBO Journal Article |
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