Solution structure of coactosin reveals structural homology to ADF/cofilin family proteins.
Coactosin is a small (MW approximately 15 kDa) evolutionarily conserved actin filament binding protein. It displays remote sequence homology to ADF/cofilin proteins and to the ADF-H domains of twinfilin and Abp1/drebrin. However, biochemical analyses have demonstrated that coactosin has a very different role in actin dynamics from the ones of ADF/cofilin, twinfilin or Abp1/drebrin. To elucidate the molecular mechanism of coactosin/actin interaction, we determined the three-dimensional structure of mouse coactosin by multidimensional NMR spectroscopy. We find that the coactosin structure is homologous to ADF/cofilin and to the ADF-H domains of twinfilin. Furthermore, the regions that have been shown to be important for actin filament interactions in ADF/cofilins are structurally conserved in coactosin suggesting that these two proteins interact with F-actin through a conserved interface. Our analysis also identifies key structural differences between these proteins that may account for the differences in biochemical activities and cellular roles of these proteins.
Program in Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki, Finland.
Maarit
M
Hellman
Ville O
VO
Paavilainen
Perttu
P
Naumanen
Pekka
P
Lappalainen
Arto
A
Annila
Perttu
P
Permi
D051339:Actin Depolymerizing Factors; D000595:Amino Acid Sequence; D024342:Amino Acids, Acidic; D024361:Amino Acids, Basic; D000818:Animals; D017124:Conserved Sequence; D051345:Destrin; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D012996:Solutions
D051339:Actin Depolymerizing Factors; D024342:Amino Acids, Acidic; D024361:Amino Acids, Basic; D051345:Destrin; D008840:Microfilament Proteins; D012996:Solutions; C485551:Cotl1 protein, mouse; C495825:Dstn protein, mouse; C485190:Twf1 protein, mouse