title: Structure and function of the interacting domains of Spire and Fmn-family formins.
abstract: 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.
authors: Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA.
authors: Christina L
authors: CL
authors: Vizcarra
authors: Barry
authors: B
authors: Kreutz
authors: Avital A
authors: AA
authors: Rodal
authors: Angela V
authors: AV
authors: Toms
authors: Jun
authors: J
authors: Lu
authors: Wei
authors: W
authors: Zheng
authors: Margot E
authors: ME
authors: Quinlan
authors: Michael J
authors: MJ
authors: Eck
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D003460:Crystallization; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005454:Fluorescence Polarization; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D009866:Oogenesis / Q000502:physiology*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary / Q000235:genetics*
chemical_list: D000199:Actins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C096354:capu protein, Drosophila; C402385:spir protein, Drosophila