Polylysine induces an antiparallel actin dimer that nucleates filament assembly: Crystal structure at 3.5-Å resolution

Michael R. Bubb, Lakshmanan Govindasamy, Elena G. Yarmola, Sergey M. Vorobiev, Steven C. Almo, Thayumanasamy Somasundaram, Michael S. Chapman, Mavis Agbandje-McKenna, Robert McKenna

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

An antiparallel actin dimer has been proposed to be an intermediate species during actin filament nucleation. We now show that latrunculin A, Ba marine natural product that inhibits actin polymerization, arrests polylysine-induced nucleation at the level of an antiparallel dimer, resulting in its accumulation. These dimers, when composed of pyrene-labeled actin subunits, give rise to a fluorescent excimer, permitting detection during polymerization in vitro. We report the crystallographic structure of the polylysine-actin-latrunculin A complex at 3.5-Å resolution. The non-crystallographic contact is consistent with a dimeric structure and confirms the antiparallel orientation of its subunits. The crystallographic contacts reveal that the mobile DNase I binding loop of one subunit of a symmetry-related antiparallel actin dimer is partially stabilized in the interface between the two subunits of a second antiparallel dimer. These results provide a potential explanation for the paradoxical nucleation of actin filaments that have exclusively parallel subunits by a dimer containing antiparallel subunits.

Original languageEnglish (US)
Pages (from-to)20999-21006
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number23
DOIs
StatePublished - Jun 7 2002
Externally publishedYes

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Polylysine
Dimers
Actins
Crystal structure
Actin Cytoskeleton
Polymerization
Nucleation
Deoxyribonuclease I
Biological Products

ASJC Scopus subject areas

  • Biochemistry

Cite this

Polylysine induces an antiparallel actin dimer that nucleates filament assembly : Crystal structure at 3.5-Å resolution. / Bubb, Michael R.; Govindasamy, Lakshmanan; Yarmola, Elena G.; Vorobiev, Sergey M.; Almo, Steven C.; Somasundaram, Thayumanasamy; Chapman, Michael S.; Agbandje-McKenna, Mavis; McKenna, Robert.

In: Journal of Biological Chemistry, Vol. 277, No. 23, 07.06.2002, p. 20999-21006.

Research output: Contribution to journalArticle

Bubb, MR, Govindasamy, L, Yarmola, EG, Vorobiev, SM, Almo, SC, Somasundaram, T, Chapman, MS, Agbandje-McKenna, M & McKenna, R 2002, 'Polylysine induces an antiparallel actin dimer that nucleates filament assembly: Crystal structure at 3.5-Å resolution', Journal of Biological Chemistry, vol. 277, no. 23, pp. 20999-21006. https://doi.org/10.1074/jbc.M201371200
Bubb, Michael R. ; Govindasamy, Lakshmanan ; Yarmola, Elena G. ; Vorobiev, Sergey M. ; Almo, Steven C. ; Somasundaram, Thayumanasamy ; Chapman, Michael S. ; Agbandje-McKenna, Mavis ; McKenna, Robert. / Polylysine induces an antiparallel actin dimer that nucleates filament assembly : Crystal structure at 3.5-Å resolution. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 23. pp. 20999-21006.
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