Structural Basis for Regulation of ESCRT-III Complexes by Lgd

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2017 Jun 1

PMID 28564595

Citations 13

Authors

Brian J McMillan

Christine Tibbe

Andrew A Drabek

Tom C M Seegar

Stephen C Blacklow

Thomas Klein

Affiliations

Soon will be listed here.

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. 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.

Citing Articles

Endosomes serve as signaling platforms for RIG-I ubiquitination and activation.

Chen K, Yang C, Shu S, Lo Y, Lee K, Wang L Sci Adv. 2024; 10(45):eadq0660.

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Structural Analysis of the ESCRT-III Regulator Lethal(2) Giant Discs/Coiled-Coil and C2 Domain-Containing Protein 1 (Lgd/CC2D1).

Breuer T, Tibbe C, Troost T, Klein T Cells. 2024; 13(14.

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Lgd regulates ESCRT-III complex accumulation at multivesicular endosomes to control intralumenal vesicle formation.

Clarke A, Lettman M, Audhya A Mol Biol Cell. 2022; 33(14):ar144.

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Using to Analyse the Human Paralogs of the ESCRT-III Core Component Shrub/CHMP4/Snf7 and Its Interactions with Members of the LGD/CC2D1 Family.

Baeumers M, Schulz K, Klein T Int J Mol Sci. 2022; 23(14).

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The ESCRT-III isoforms CHMP2A and CHMP2B display different effects on membranes upon polymerization.

Alqabandi M, De Franceschi N, Maity S, Miguet N, Bally M, Roos W BMC Biol. 2021; 19(1):66.

PMID: 33832485 PMC: 8033747. DOI: 10.1186/s12915-021-00983-9.

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