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.
Hellman
Maarit
M
Program in Structural Biology and Biophysics, Institute of Biotechnology, University of Helsinki, Finland.
Paavilainen
Ville O
VO
Naumanen
Perttu
P
Lappalainen
Pekka
P
Annila
Arto
A
Permi
Perttu
P
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