RT Journal Article
SR Electronic
T1 The ESCRT-III proteins IST1 and CHMP1B assemble around nucleic acids
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 386532
DO 10.1101/386532
A1 Nathaniel Talledge
A1 John McCullough
A1 Dawn Wenzel
A1 Henry C. Nguyen
A1 Matthew S. Lalonde
A1 Monika Bajorek
A1 Jack Skalicky
A1 Adam Frost
A1 Wesley I. Sundqust
YR 2018
UL http://biorxiv.org/content/early/2018/08/07/386532.abstract
AB ESCRT-III proteins can promote inside-out or outside-in membrane tubulation and fission. In addition, several observations suggest that ESCRT factors may also associate with nucleic acids during development, different stages of the cell cycle, and during retro-transposition of parasitic nucleic acids like LINE1 elements. Two ESCRT-III subunits, IST1 (aka CHMP8) and CHMP1B, can coassemble as an external protein coat around liposomes in vitro and around recycling endosomal tubules in living cells. Here we show that recombinant IST1 and CHMP1B can also copolymerize into double stranded filaments that surround nucleic acids. Electron cryo-microscopy reconstructions of nucleic acid-bound IST1-CHMP1B copolymers revealed that the polynucleotides track along a binding groove formed between filaments of the inner CHMP1B strand. The well-ordered structures also reveal that the C-terminal tails of CHMP1B subunits extrude through the outer IST1 layer to the tube exterior. As a result, the MIT domain binding motifs of both CHMP1B and IST1 are arrayed on the outer surface of the copolymer, where they could bind and recruit MIT domain-containing co-factors, such as the SPASTIN ATPase or the USP8 ubiquitin protease. Our structure raises the possibility that ESCRT-III proteins may form nucleic acid complexes in mammalian cells.