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Title: Structure and membrane remodeling activity of ESCRT-III helical polymers

Journal Article · · Science

The endosomal sorting complexes required for transport (ESCRT) proteins mediate fundamental membrane remodeling events that require stabilizing negative membrane curvature. These include endosomal intralumenal vesicle formation, HIV budding, nuclear envelope closure, and cytokinetic abscission. ESCRT-III subunits perform key roles in these processes by changing conformation and polymerizing into membrane-remodeling filaments. Here, we report the 4 angstrom resolution cryogenic electron microscopy reconstruction of a one-start, double-stranded helical copolymer composed of two different human ESCRT-III subunits, charged multivesicular body protein 1B (CHMP1B) and increased sodium tolerance 1 (IST1). The inner strand comprises "open" CHMP1B subunits that interlock in an elaborate domain-swapped architecture and is encircled by an outer strand of "closed" IST1 subunits. Unlike other ESCRT-III proteins, CHMP1B and IST1 polymers form external coats on positively curved membranes in vitro and in vivo. Our analysis suggests how common ESCRT-III filament architectures could stabilize different degrees and directions of membrane curvature.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
National Institutes of Health (NIH); National Science Foundation (NSF); USDOE Office of Science (SC)
Grant/Contract Number:
AC02-05CH11231; DGE-1143954; 2P50GM082545-06; R01GM112080; R01AI051174; 1DP2GM110772-01; 1P01 GM063210; R01GM076686; R01NS050717
OSTI ID:
1355856
Alternate ID(s):
OSTI ID: 1257996; OSTI ID: 1378702
Journal Information:
Science, Journal Name: Science Vol. 350 Journal Issue: 6267; ISSN 0036-8075
Publisher:
American Association for the Advancement of Science (AAAS)Copyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 163 works
Citation information provided by
Web of Science

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