The limits of promiscuity: isoform-specific dimerization of filamins.
Filamins are a family of actin cross-linking proteins that are primarily localized in the cortical cytoplasm of all mammalian cells. Until now, three major isoforms (filamins a, b, and c) have been identified, that were shown to be differentially expressed and/or localized in different tissues. An amino-terminal double CH-domain actin binding domain, and a dimerization region in the carboxy-terminal portion of the protein are the molecular basis for its actin cross-linking activity. Chemical cross-linking of bacterially expressed recombinant proteins was used to demonstrate that in all three filamin isoforms the most carboxy-terminally situated immunoglobulinlike domain is required and sufficient for dimerization. The efficiency of the dimerization was increased upon inclusion of the preceding hinge 2 region, indicating a function for this region in the regulation of dimerization. By mixing recombinant proteins derived from different filamin isoforms, we found that heterodimer formation is possible between filamins b and c but not between filamin a and the other two filamins. This selectivity of dimerization might provide a further molecular explanation for the differential intracellular sorting of filamin isoforms and their distinct properties.
Himmel
Mirko
M
Department of Cell Biology, University of Potsdam, Lennéstrasse 7a, 14471 Potsdam, Germany.
Van Der Ven
Peter F M
PF
Stöcklein
Walter
W
Fürst
Dieter O
DO
D000595:Amino Acid Sequence; D003285:Contractile Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D003432:Cross-Linking Reagents / Q000737:chemistry; D019281:Dimerization; D004926:Escherichia coli / Q000235:genetics; D064448:Filamins; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D011189:Potassium Chloride / Q000737:chemistry; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D020349:Surface Plasmon Resonance
D003285:Contractile Proteins; D003432:Cross-Linking Reagents; D064448:Filamins; D007136:Immunoglobulins; D008840:Microfilament Proteins; D010446:Peptide Fragments; D020033:Protein Isoforms; D011994:Recombinant Proteins; D011189:Potassium Chloride