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Biomolecular mimicry in the actin cytoskeleton: mechanisms underlying the cytotoxicity of kabiramide C and related macrolides.

ABSTRACT: This study characterizes the interactions between kabiramide C (KabC) and related macrolides and actin and establishes the mechanisms that underlie their inhibition of actin filament dynamics and cytotoxicity. The G-actin-KabC complex is formed through a two-step binding reaction and is extremely stable and long-lived. Competition-binding studies show that KabC binds to the same site on G-actin as Gelsolin domain 1 and CapG. KabC also binds to protomers within F-actin and results in the severing and capping of the (+) end; these studies suggest that free KabC and related macrolides act as biomimetics of Gelsolin. The G-actin-KabC complex binds to the (+) end of a growing filament, where it functions as a novel, unregulated, (+)-end capper and is largely responsible for the inhibition of motility and cytokinesis in approximately 10 -100 nM KabC-treated cells. KabC and related macrolides are useful probes to study the regulation of the actin filament (+) end and may lead to new therapies to treat diseases of the actin cytoskeleton.

SUBMITTER: Tanaka J

PROVIDER: S-EPMC283510 | biostudies-literature | 2003 Nov

REPOSITORIES: biostudies-literature

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Biomolecular mimicry in the actin cytoskeleton: mechanisms underlying the cytotoxicity of kabiramide C and related macrolides.

Tanaka Junichi J Yan Yuling Y Choi Jeongeun J Bai Jihong J Klenchin Vadim A VA Rayment Ivan I Marriott Gerard G

Proceedings of the National Academy of Sciences of the United States of America 20031111 24

This study characterizes the interactions between kabiramide C (KabC) and related macrolides and actin and establishes the mechanisms that underlie their inhibition of actin filament dynamics and cytotoxicity. The G-actin-KabC complex is formed through a two-step binding reaction and is extremely stable and long-lived. Competition-binding studies show that KabC binds to the same site on G-actin as Gelsolin domain 1 and CapG. KabC also binds to protomers within F-actin and results in the severing ...[more]

PMID: 14612571

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Dataset Information

Biomolecular mimicry in the actin cytoskeleton: mechanisms underlying the cytotoxicity of kabiramide C and related macrolides.

Publications

Biomolecular mimicry in the actin cytoskeleton: mechanisms underlying the cytotoxicity of kabiramide C and related macrolides.

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