Structural basis for vertebrate filamin dimerization.
Filamins are essential in cell motility and many developmental processes. They are large actin cross linking proteins that contain actin binding domains in their N termini and a long rod region constructed from 24 tandem Ig domains. Dimerization is crucial for the actin crosslinking function of filamins and requires the most C-terminal Ig domain. We describe here the crystal structure of this 24th Ig domain (Ig24) of human filamin C and show how it mediates dimerization. The dimer interface is novel and quite different to that seen in the Dictyostelium discoideum filamin analog. The sequence signature of the dimerization interface suggests that the C-terminal domains of all vertebrate filamins share the same dimerization mechanism. Furthermore, we show that point mutations in the dimerization interface disrupt the dimer and that the dissociation constant for recombinant Ig24 is in the micromolar range.
Pudas
Regina
R
Biocenter Oulu and Department of Biochemistry, University of Oulu, Finland.
Kiema
Tiila-Riikka
TR
Butler
P Jonathan G
PJ
Stewart
Murray
M
Ylänne
Jari
J
D000199:Actins / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002850:Chromatography, Gel; D002942:Circular Dichroism; D003285:Contractile Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000737:chemistry; D018360:Crystallography, X-Ray; D004023:Dictyostelium / Q000737:chemistry; D019281:Dimerization; D064448:Filamins; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008840:Microfilament Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014461:Ultracentrifugation; D014714:Vertebrates
D000199:Actins; D003285:Contractile Proteins; D003432:Cross-Linking Reagents; D064448:Filamins; D008840:Microfilament Proteins; D020033:Protein Isoforms; D001224:Aspartic Acid