Structure and membrane remodeling activity of ESCRT-III helical polymers

Details

• Alternative Title:
  Science
• Personal Author:
  McCullough, John ; Clippinger, Amy K. ; Talledge, Nathaniel ; Skowyra, Michael L. ; Saunders, Marissa G. ; Naismith, Teresa V. ; Colf, Leremy A. ; Afonine, Pavel ; Arthur, Christopher ; Sundquist, Wesley I. ; Hanson, Phyllis I. ; Frost, Adam
• Description:
  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.
• Subjects:
  Biopolymers Cell Membrane Cryoelectron Microscopy Endosomal Sorting Complexes Required For Transport Humans Oncogene Proteins Protein Structure, Secondary Protein Structure, Tertiary
• Source:
  Science. 350(6267):1548-1551
• Pubmed ID:
  26634441
• Pubmed Central ID:
  PMC4684769
• Document Type:
  Journal Article
• Funding:
  P50 GM082545/GM/NIGMS NIH HHSUnited States/ ; P41 RR17573/RR/NCRR NIH HHSUnited States/ ; R01AI051174/AI/NIAID NIH HHSUnited States/ ; 1P01 GM063210/GM/NIGMS NIH HHSUnited States/ ; R01 GM112080/GM/NIGMS NIH HHSUnited States/ ; R01GM076686/GM/NIGMS NIH HHSUnited States/ ; R01 AI051174/AI/NIAID NIH HHSUnited States/ ; P41 RR017573/RR/NCRR NIH HHSUnited States/ ; R01 GM076686/GM/NIGMS NIH HHSUnited States/ ; 2P50GM082545-06/GM/NIGMS NIH HHSUnited States/ ; R01NS050717/NS/NINDS NIH HHSUnited States/ ; P01 GM063210/GM/NIGMS NIH HHSUnited States/ ; R01 NS050717/NS/NINDS NIH HHSUnited States/ ; R01GM112080/GM/NIGMS NIH HHSUnited States/ ; 1DP2GM110772-01/DP/NCCDPHP CDC HHSUnited States/ ; DP2 GM110772/GM/NIGMS NIH HHSUnited States/
• Volume:
  350
• Issue:
  6267
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:f4cadab81953a3f0ce8e739868c5f4aa28ad5b182546614b1251a8afffca70e4
• Download URL:
  https://stacks.cdc.gov/view/cdc/36923/cdc_36923_DS1.pdf
• File Type:
  [PDF - 2.03 MB ]