A pseudoatomic model of the dynamin polymer identifies a hydrolysis-dependent powerstroke

Joshua S. Chappie, Jason A. Mears, Shunming Fang, Marilyn Leonard, Sandra L. Schmid, Ronald A. Milligan, Jenny E. Hinshaw, Fred Dyda

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

The GTPase dynamin catalyzes membrane fission by forming a collar around the necks of clathrin-coated pits, but the specific structural interactions and conformational changes that drive this process remain a mystery. We present the GMPPCP-bound structures of the truncated human dynamin 1 helical polymer at 12.2 and a fusion protein, GG, linking human dynamin 1's catalytic G domain to its GTPase effector domain (GED) at 2.2 . The structures reveal the position and connectivity of dynamin fragments in the assembled structure, showing that G domain dimers only form between tetramers in sequential rungs of the dynamin helix. Using chemical crosslinking, we demonstrate that dynamin tetramers are made of two dimers, in which the G domain of one molecule interacts in trans with the GED of another. Structural comparison of GG GMPPCP to the GG transition-state complex identifies a hydrolysis-dependent powerstroke that may play a role in membrane-remodeling events necessary for fission.

Original languageEnglish (US)
Pages (from-to)209-222
Number of pages14
JournalCell
Volume147
Issue number1
DOIs
StatePublished - Sep 30 2011

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Dynamins
Hydrolysis
GTP Phosphohydrolases
Polymers
Dynamin I
Dimers
Membranes
Clathrin
Crosslinking
Catalytic Domain
Neck
Fusion reactions
Molecules
Proteins
5'-guanylylmethylenebisphosphonate

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Chappie, J. S., Mears, J. A., Fang, S., Leonard, M., Schmid, S. L., Milligan, R. A., ... Dyda, F. (2011). A pseudoatomic model of the dynamin polymer identifies a hydrolysis-dependent powerstroke. Cell, 147(1), 209-222. https://doi.org/10.1016/j.cell.2011.09.003

A pseudoatomic model of the dynamin polymer identifies a hydrolysis-dependent powerstroke. / Chappie, Joshua S.; Mears, Jason A.; Fang, Shunming; Leonard, Marilyn; Schmid, Sandra L.; Milligan, Ronald A.; Hinshaw, Jenny E.; Dyda, Fred.

In: Cell, Vol. 147, No. 1, 30.09.2011, p. 209-222.

Research output: Contribution to journalArticle

Chappie, JS, Mears, JA, Fang, S, Leonard, M, Schmid, SL, Milligan, RA, Hinshaw, JE & Dyda, F 2011, 'A pseudoatomic model of the dynamin polymer identifies a hydrolysis-dependent powerstroke', Cell, vol. 147, no. 1, pp. 209-222. https://doi.org/10.1016/j.cell.2011.09.003
Chappie, Joshua S. ; Mears, Jason A. ; Fang, Shunming ; Leonard, Marilyn ; Schmid, Sandra L. ; Milligan, Ronald A. ; Hinshaw, Jenny E. ; Dyda, Fred. / A pseudoatomic model of the dynamin polymer identifies a hydrolysis-dependent powerstroke. In: Cell. 2011 ; Vol. 147, No. 1. pp. 209-222.
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