3VHX

The crystal structure of Arf6-MKLP1 (Mitotic kinesin-like protein 1) complex

Summary for 3VHX

• Entry DOI: 10.2210/pdb3vhx/pdb
• Descriptor: ADP-ribosylation factor 6, Kinesin-like protein KIF23, GUANOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: small gtpase, gtp binding, flemming body, cytokinesis, cell cycle-signaling protein complex, cell cycle/signaling protein
• Biological source: Mus musculus (mouse); More
• Cellular location: Golgi apparatus (By similarity): P62331; Nucleus: Q02241
• Total number of polymer chains: 8
• Total formula weight: 136306.67

Authors

Makyio, H.,Takei, T.,Ohgi, H.,Takahashi, S.,Takatsu, H.,Ueda, T.,Kanaho, Y.,Xie, Y.,Shin, H.W.,Kamikubo, H.,Kataoka, M.,Kawasaki, M.,Kato, R.,Wakatsuki, S.,Nakayama, K. (deposition date: 2011-09-12, release date: 2012-05-16, Last modification date: 2023-11-08)

Primary citation

Makyio, H.,Ohgi, M.,Takei, T.,Takahashi, S.,Takatsu, H.,Katoh, Y.,Hanai, A.,Ueda, T.,Kanaho, Y.,Xie, Y.,Shin, H.W.,Kamikubo, H.,Kataoka, M.,Kawasaki, M.,Kato, R.,Wakatsuki, S.,Nakayama, K.
Structural basis for Arf6-MKLP1 complex formation on the Flemming body responsible for cytokinesis
Embo J., 31:2590-2603, 2012

PubMed 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 2:2 heterotetramer containing an extended β-sheet composed of 22 β-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.

PubMed: 22522702
DOI: 10.1038/emboj.2012.89

Experimental method

X-RAY DIFFRACTION (2.81 Å)