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Membrane constriction and thinning by sequential ESCRT-III polymerization.

Henry C Nguyen1, Nathaniel Talledge1,2,3, John McCullough2

  • 1Department of Biochemistry & Biophysics, University of California, San Francisco, San Francisco, CA, USA.

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|April 7, 2020
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Summary
This summary is machine-generated.

Endosomal sorting complexes required for transport (ESCRT) proteins remodel membranes. New structures reveal how CHMP1B and IST1 filaments sequentially polymerize to shape positively curved membranes, driving tubulation and fission.

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Area of Science:

  • Cell Biology
  • Structural Biology
  • Biochemistry

Background:

  • Endosomal sorting complexes required for transport (ESCRT) proteins are crucial for membrane remodeling.
  • While typically associated with negative membrane curvature, some ESCRT-III proteins also shape positively curved membranes.
  • The structural mechanisms underlying ESCRT-III mediated positive membrane curvature remain unclear.

Purpose of the Study:

  • To elucidate the structural basis of positive membrane curvature remodeling by ESCRT-III proteins.
  • To understand the mechanism by which CHMP1B and IST1 cooperate to shape membranes.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) was used to determine the structures of CHMP1B-only, CHMP1B + IST1, and IST1-only filaments.
  • Analysis of membrane-bound filaments to understand their interaction with lipid bilayers.

Main Results:

  • CHMP1B polymerizes into a single-stranded helical filament, inducing moderate membrane tubulation.
  • IST1 assembles a second strand onto CHMP1B, leading to further membrane constriction towards fission.
  • This sequential polymerization process thins the lipid bilayer, facilitating membrane fission.

Conclusions:

  • A two-component, sequential polymerization mechanism involving CHMP1B and IST1 drives membrane tubulation and constriction.
  • These ESCRT-III proteins actively shape positively curved membranes, lowering the energy barrier for membrane fission.
  • The findings provide structural insights into ESCRT-mediated membrane remodeling events.