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

doi:10.1016/j.str.2006.01.012

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 journal › Article › peer-review

27 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 language	English (US)
Pages (from-to)	661-671
Number of pages	11
Journal	Structure
Volume	14
Issue number	4
DOIs	https://doi.org/10.1016/j.str.2006.01.012
State	Published - Apr 2006
Externally published	Yes

Keywords

PROTEINS

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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10.1016/j.str.2006.01.012

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@article{ebe12daba2be48ee98a68330cdce810c,

title = "The Endosome-Associated Protein Hrs Is Hexameric and Controls Cargo Sorting as a {"}Master Molecule{"}",

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.",

keywords = "PROTEINS",

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

note = "Funding Information: We thank Christian M.T. Spahn for helpful discussions. This work was supported, in part, by National Institutes of Health Grants MH 58920 (to A.J.B.) and NS 43258 and GM 60635 (to P.A.P.). ",

year = "2006",

month = apr,

doi = "10.1016/j.str.2006.01.012",

language = "English (US)",

volume = "14",

pages = "661--671",

journal = "Structure",

issn = "0969-2126",

publisher = "Cell Press",

number = "4",

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T1 - The Endosome-Associated Protein Hrs Is Hexameric and Controls Cargo Sorting as a "Master Molecule"

AU - Pullan, Lee

AU - Mullapudi, Srinivas

AU - Huang, Zhong

AU - Baldwin, Philip R.

AU - Chin, Christopher

AU - Sun, Wei

AU - Tsujimoto, Susan

AU - Kolodziej, Steven J.

AU - Stoops, James K.

AU - Lee, J. Ching

AU - Waxham, M. Neal

AU - Bean, Andrew J.

AU - Penczek, Pawel A.

N1 - Funding Information: We thank Christian M.T. Spahn for helpful discussions. This work was supported, in part, by National Institutes of Health Grants MH 58920 (to A.J.B.) and NS 43258 and GM 60635 (to P.A.P.).

PY - 2006/4

Y1 - 2006/4

N2 - 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.

AB - 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.

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

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Keywords

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