Article

Crystal structure of human DAAM1 formin homology 2 domain.

Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan.
Genes to Cells (impact factor: 2.68). 12/2007; 12(11):1255-65. DOI:10.1111/j.1365-2443.2007.01132.x pp.1255-65
Source: PubMed

ABSTRACT Reorganization of the actin filament is an essential process for cell motility, cell-cell attachment and intracellular transport. Formin proteins promote nucleation and elongation of the actin filament, and thus are key regulators for this process. The formin homology 2 (FH2) domain forms a head-to-tail ring-shaped dimer, and processively moves towards the barbed end. Dishevelled-associated activator of morphogenesis (DAAM) is a Rho-regulated formin implicated in neuronal development. Here, we present the crystal structure of human DAAM1 FH2 dimer at 2.8 A resolution. This is the first dimeric structure of the mammalian formin. The core structure of human DAAM1 is similar to those of mouse mDia1 and yeast Bni1p, whereas the orientations of the FH2 dimeric rings are different between human DAAM1 and yeast Bni1p, despite their similar dimer interactions. This difference supports the previous prediction that the dimer architecture of the formin is highly flexible in the actin-free state. The results of the actin assembly assays using the DAAM1 mutants demonstrated that the length of the linker connecting the N-terminal domain and the core region is crucial for the activity.

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    Article: DAAM family members leading a novel path into formin research.
    Andreas Prokop, Natalia Sánchez-Soriano, Catarina Gonçalves-Pimentel, Imre Molnár, Tibor Kalmár, József Mihály
    [show abstract] [hide abstract]
    ABSTRACT: Formins are an important and evolutionarily well conserved class of actin binding proteins with essential biological functions. Although their molecular roles in actin regulation have been clearly demonstrated in vitro, their functions at the cellular or organism levels are still poorly understood. To illustrate this problem, but also to demonstrate potential ways forward, we focus here on the DAAM group of formins. In vertebrates, DAAM group members have been demonstrated to be important regulators of cellular and tissue morphogenesis but, as for all formins, the molecular mechanisms underlying these morphogenetic functions remain to be uncovered. The genome of the fruitfly Drosophila encodes a single DAAM gene that is evolutionarily highly conserved. Recent work on dDAAM has already provided a unique combination of observations and experimental opportunities unrivalled by any other Drosophila formin. These comprise in vitro actin polymerisation assays, subcellular studies in culture and in vivo, and a range of developmental phenotypes revealing a role in tracheal morphogenesis, axonal growth and muscle organization. At all these levels, future work on dDAAM will capitalize on the power of fly genetics, raising unique opportunities to advance our understanding of dDAAM at the systems level, with obvious implications for other formins.
    Communicative & integrative biology 01/2011; 4(5):538-42.
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Keywords

actin assembly assays
 
actin-free state
 
DAAM1 mutants
 
Dishevelled-associated activator
 
essential process
 
FH2 dimeric rings
 
formin homology 2
 
Formin proteins
 
human DAAM1
 
human DAAM1 FH2 dimer
 
intracellular transport
 
mammalian formin
 
mouse mDia1
 
N-terminal domain
 
neuronal development
 
previous prediction
 
processively moves
 
Rho-regulated formin
 
similar dimer interactions
 
yeast Bni1p