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Publication : Structural basis for Arf6-MKLP1 complex formation on the Flemming body responsible for cytokinesis.

First Author  Makyio H Year  2012
Journal  EMBO J Volume  31
Issue  11 Pages  2590-603
PubMed ID  22522702 Mgi Jnum  J:184675
Mgi Id  MGI:5426069 Doi  10.1038/emboj.2012.89
Citation  Makyio H, et al. (2012) Structural basis for Arf6-MKLP1 complex formation on the Flemming body responsible for cytokinesis. EMBO J 31(11):2590-603
abstractText  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 2:2 heterotetramer containing an extended beta-sheet composed of 22 beta-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.
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