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

Publication Type:

Journal Article

Authors:

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

Source:

Proc Natl Acad Sci U S A, Volume 108, Issue 29, p.11884-9 (2011)

Keywords:

Actins, Animals, Crystallization, Drosophila melanogaster, Drosophila Proteins, Fluorescence Polarization, Humans, Microfilament Proteins, Models, Molecular, Nerve Tissue Proteins, Oogenesis, Protein Conformation, Protein Structure, Tertiary

Abstract:

<p>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.</p>