The Endosome-Associated Protein Hrs Is Hexameric and Controls Cargo Sorting as a "Master Molecule"

Lee Pullan, Srinivas Mullapudi, Zhong Huang, Philip R. Baldwin, Christopher Chin, Wei Sun, Susan Tsujimoto, Steven J. Kolodziej, James K. Stoops, J. Ching Lee, M. Neal Waxham, Andrew J. Bean, Pawel A. Penczek

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

The structure of the endosomal-associated protein, Hrs, has been determined with cryo-electron microscopy. Hrs interacts with a number of proteins, including SNAP-25 and STAM1, forming a complex that binds ubiquitin moieties. Analytical ultracentrifugation studies revealed that Hrs exists as a hexamer. The symmetry and the structure of the hexameric form of Hrs were determined with the single-particle reconstruction method. Hrs comprises three antiparallel dimers with a central core and distinct caps on either end. Crystal structures of VHS and FYVE domains fit into the Hrs end caps in the EM density map. Thus, the location of domains that interact with the endosomal membrane, the VHS, FYVE, and C-terminal domains, facilitates the anchorage of Hrs to the membrane, initiating the functional processes of Hrs on the endosome. Based on our model, the Hrs hexamer interacts with the membrane and acts as a "master molecule" that presents multiple sites for protein binding.

Original languageEnglish (US)
Pages (from-to)661-671
Number of pages11
JournalStructure
Volume14
Issue number4
DOIs
StatePublished - Apr 1 2006

Keywords

  • PROTEINS

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Pullan, L., Mullapudi, S., Huang, Z., Baldwin, P. R., Chin, C., Sun, W., Tsujimoto, S., Kolodziej, S. J., Stoops, J. K., Lee, J. C., Waxham, M. N., Bean, A. J., & Penczek, P. A. (2006). The Endosome-Associated Protein Hrs Is Hexameric and Controls Cargo Sorting as a "Master Molecule". Structure, 14(4), 661-671. https://doi.org/10.1016/j.str.2006.01.012