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Structure and function of the interacting domains of Spire and Fmn-family formins

2011; National Academy of Sciences; Volume: 108; Issue: 29 Linguagem: Inglês

10.1073/pnas.1105703108

1091-6490

Christina L. Vizcarra, Barry Kreutz, Avital A. Rodal, Angela V. Toms, Jun Lu, Wei Zheng, Margot E. Quinlan, Michael J. Eck,

Neurobiology and Insect Physiology Research

Evidence for cooperation between actin nucleators is growing. The WH2-containing nucleator Spire and the formin Cappuccino interact directly, and both are essential for assembly of an actin mesh during Drosophila oogenesis. Their interaction requires the kinase noncatalytic C-lobe domain (KIND) domain of Spire and the C-terminal tail of the formin. Here we describe the crystal structure of the KIND domain of human Spir1 alone and in complex with the tail of Fmn2, a mammalian ortholog of Cappuccino. The KIND domain is structurally similar to the C-lobe of protein kinases. The Fmn2 tail is coordinated in an acidic cleft at the base of the domain that appears to have evolved via deletion of a helix from the canonical kinase fold. Our functional analysis of Cappuccino reveals an unexpected requirement for its tail in actin assembly. In addition, we find that the KIND/tail interaction blocks nucleation by Cappuccino and promotes its displacement from filament barbed ends providing insight into possible modes of cooperation between Spire and Cappuccino.