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Title: Structural Basis for Regulation of ESCRT-III Complexes by Lgd

Abstract

The ESCRT-III complex induces outward membrane budding and fission through homotypic polymerization of its core component Shrub/CHMP4B. Shrub activity is regulated by its direct interaction with a protein called Lgd in flies, or CC2D1A or B in humans. Here, we report the structural basis for this interaction and propose a mechanism for regulation of polymer assembly. The isolated third DM14 repeat of Lgd binds Shrub, and an Lgd fragment containing only this DM14 repeat and its C-terminal C2 domain is sufficient for in vivo function. Here, the DM14 domain forms a helical hairpin with a conserved, positively charged tip, that, in the structure of a DM14 domain-Shrub complex, occupies a negatively charged surface of Shrub that is otherwise used for homopolymerization. Lgd mutations at this interface disrupt its function in flies, confirming functional importance. Together, these data argue that Lgd regulates ESCRT activity by controlling access to the Shrub self-assembly surface.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Scientific User Facilities Division; National Institute of General Medical Sciences; National Institutes of Health (NIH)
OSTI Identifier:
1394846
Alternate Identifier(s):
OSTI ID: 1368301
Grant/Contract Number:  
AC02-06CH11357; 5 P01 CA119070; 5 R01 CA092433; P41 GM103403
Resource Type:
Published Article
Journal Name:
Cell Reports
Additional Journal Information:
Journal Name: Cell Reports Journal Volume: 19 Journal Issue: 9; Journal ID: ISSN 2211-1247
Publisher:
Elsevier
Country of Publication:
Netherlands
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Snf7; Shrub; membrane fission; lethal giant discs; CC2D1A; CC2D1B; CHMP4B; DM14 domain; multivesicular body

Citation Formats

McMillan, Brian J., Tibbe, Christine, Drabek, Andrew A., Seegar, Tom C. M., Blacklow, Stephen C., and Klein, Thomas. Structural Basis for Regulation of ESCRT-III Complexes by Lgd. Netherlands: N. p., 2017. Web. doi:10.1016/j.celrep.2017.05.026.
McMillan, Brian J., Tibbe, Christine, Drabek, Andrew A., Seegar, Tom C. M., Blacklow, Stephen C., & Klein, Thomas. Structural Basis for Regulation of ESCRT-III Complexes by Lgd. Netherlands. doi:10.1016/j.celrep.2017.05.026.
McMillan, Brian J., Tibbe, Christine, Drabek, Andrew A., Seegar, Tom C. M., Blacklow, Stephen C., and Klein, Thomas. Mon . "Structural Basis for Regulation of ESCRT-III Complexes by Lgd". Netherlands. doi:10.1016/j.celrep.2017.05.026.
@article{osti_1394846,
title = {Structural Basis for Regulation of ESCRT-III Complexes by Lgd},
author = {McMillan, Brian J. and Tibbe, Christine and Drabek, Andrew A. and Seegar, Tom C. M. and Blacklow, Stephen C. and Klein, Thomas},
abstractNote = {The ESCRT-III complex induces outward membrane budding and fission through homotypic polymerization of its core component Shrub/CHMP4B. Shrub activity is regulated by its direct interaction with a protein called Lgd in flies, or CC2D1A or B in humans. Here, we report the structural basis for this interaction and propose a mechanism for regulation of polymer assembly. The isolated third DM14 repeat of Lgd binds Shrub, and an Lgd fragment containing only this DM14 repeat and its C-terminal C2 domain is sufficient for in vivo function. Here, the DM14 domain forms a helical hairpin with a conserved, positively charged tip, that, in the structure of a DM14 domain-Shrub complex, occupies a negatively charged surface of Shrub that is otherwise used for homopolymerization. Lgd mutations at this interface disrupt its function in flies, confirming functional importance. Together, these data argue that Lgd regulates ESCRT activity by controlling access to the Shrub self-assembly surface.},
doi = {10.1016/j.celrep.2017.05.026},
journal = {Cell Reports},
number = 9,
volume = 19,
place = {Netherlands},
year = {2017},
month = {5}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1016/j.celrep.2017.05.026

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Cited by: 6 works
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