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

Nature Structural & Molecular Biology volume 13, pages 10291030 (2006) | Download Citation

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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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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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Affiliations

  1. Department of Biochemistry, University of Utah, Salt Lake City, Utah 84112-5650, 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, New York 11973-5000, USA.

    • Howard Robinson

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Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Christopher P Hill or Wesley I Sundquist.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Alignment of EAP45/Vps36p GLUE domains.

  2. 2.

    Supplementary Fig. 2

    Comparisons of the human EAP45 and yeast Vps36p GLUE domains.

  3. 3.

    Supplementary Table 1

    Data collection and refinement statistics for the EAP45 GLUE–Ub complex.

  4. 4.

    Supplementary Table 2

    Binding affinities of different EAP45 GLUE–Ub complexes.

  5. 5.

    Supplementary Methods

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DOI

https://doi.org/10.1038/nsmb1160

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