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Structural basis for ubiquitin recognition by the human ESCRT-II EAP45 GLUE domain

Nature Structural & Molecular Biology volume 13, pages 1029–1030 (2006)Cite this article

Abstract

The ESCRT-I and ESCRT-II complexes help sort ubiquitinated proteins into vesicles that accumulate within multivesicular bodies (MVBs). Crystallographic and biochemical analyses reveal that the GLUE domain of the human ESCRT-II EAP45 (also called VPS36) subunit is a split pleckstrin-homology domain that binds ubiquitin along one edge of the β-sandwich. The structure suggests how human ESCRT-II can couple recognition of ubiquitinated cargoes and endosomal phospholipids during MVB protein sorting.

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Figure 1: Structure of the EAP45 GLUE–Ub complex.
Figure 2: Biosensor binding analyses of the EAP45 GLUE–Ub interaction.

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Acknowledgements

Biosensor analyses, protein sequencing and mass spectrometry were performed at University of Utah core facilities, and we also thank I. Jafri for technical assistance. This work was supported by US National Institutes of Health grants to C.P.H. (GM66521) and W.I.S. (AI51174). The National Synchrotron Light Source is funded by the US National Center for Research Resources, by the US Department of Energy, Office of Basic Energy Sciences and by the US National Institutes of Health.

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Authors and Affiliations

  1. Department of Biochemistry, University of Utah, Salt Lake City, 84112-5650, Utah, USA

    Steven L Alam, Charles Langelier, Frank G Whitby, Sajjan Koirala, Christopher P Hill & Wesley I Sundquist

  2. Biology Department, 463 Brookhaven National Laboratory, Upton, 11973-5000, New York, USA

    Howard Robinson

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  1. Steven L Alam
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  2. Charles Langelier
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  3. Frank G Whitby
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  6. Christopher P Hill
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  7. Wesley I Sundquist
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Corresponding authors

Correspondence to Christopher P Hill or Wesley I Sundquist.

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Supplementary information

Supplementary Fig. 1

Alignment of EAP45/Vps36p GLUE domains. (PDF 928 kb)

Supplementary Fig. 2

Comparisons of the human EAP45 and yeast Vps36p GLUE domains. (PDF 1677 kb)

Supplementary Table 1

Data collection and refinement statistics for the EAP45 GLUE–Ub complex. (PDF 20 kb)

Supplementary Table 2

Binding affinities of different EAP45 GLUE–Ub complexes. (PDF 66 kb)

Supplementary Methods (PDF 103 kb)

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Alam, S., Langelier, C., Whitby, F. et al. Structural basis for ubiquitin recognition by the human ESCRT-II EAP45 GLUE domain. Nat Struct Mol Biol 13, 1029–1030 (2006). https://doi.org/10.1038/nsmb1160

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