Structural basis for Arf6-MKLP1 complex formation on the Flemming body responsible for cytokinesis.
EMBO J
; 31(11): 2590-603, 2012 May 30.
Article
en En
| MEDLINE
| ID: mdl-22522702
ABSTRACT
A small GTPase, Arf6, is involved in cytokinesis by localizing to the Flemming body (the midbody). However, it remains unknown how Arf6 contributes to cytokinesis. Here, we demonstrate that Arf6 directly interacts with mitotic kinesin-like protein 1 (MKLP1), a Flemming body-localizing protein essential for cytokinesis. The crystal structure of the Arf6-MKLP1 complex reveals that MKLP1 forms a homodimer flanked by two Arf6 molecules, forming a 22 heterotetramer containing an extended ß-sheet composed of 22 ß-strands that spans the entire heterotetramer, suitable for interaction with a concave membrane surface at the cleavage furrow. We show that, during cytokinesis, Arf6 is first accumulated around the cleavage furrow and, prior to abscission, recruited onto the Flemming body via interaction with MKLP1. We also show by structure-based mutagenesis and siRNA-mediated knockdowns that the complex formation is required for completion of cytokinesis. A model based on these results suggests that the Arf6-MKLP1 complex plays a crucial role in cytokinesis by connecting the microtubule bundle and membranes at the cleavage plane.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Factores de Ribosilacion-ADP
/
Citocinesis
/
Proteínas Asociadas a Microtúbulos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
EMBO J
Año:
2012
Tipo del documento:
Article
País de afiliación:
Japón