Atomic structures of two novel immunoglobulin-like domain pairs in the actin cross-linking protein filamin.
Filamins are actin filament cross-linking proteins composed of an N-terminal actin-binding domain and 24 immunoglobulin-like domains (IgFLNs). Filamins interact with numerous proteins, including the cytoplasmic domains of plasma membrane signaling and cell adhesion receptors. Thereby filamins mechanically and functionally link the cell membrane to the cytoskeleton. Most of the interactions have been mapped to the C-terminal IgFLNs 16-24. Similarly, as with the previously known compact domain pair of IgFLNa20-21, the two-domain fragments IgFLNa16-17 and IgFLNa18-19 were more compact in small angle x-ray scattering analysis than would be expected for two independent domains. Solution state NMR structures revealed that the domain packing in IgFLNa18-19 resembles the structure of IgFLNa20-21. In both domain pairs the integrin-binding site is masked, although the details of the domain-domain interaction are partly distinct. The structure of IgFLNa16-17 revealed a new domain packing mode where the adhesion receptor binding site of domain 17 is not masked. Sequence comparison suggests that similar packing of three tandem filamin domain pairs is present throughout the animal kingdom, and we propose that this packing is involved in the regulation of filamin interactions through a mechanosensor mechanism.
Heikkinen
Outi K
OK
Department of Chemistry, University of Helsinki, FI-00014 Helsinki, Finland.
Ruskamo
Salla
S
Konarev
Peter V
PV
Svergun
Dmitri I
DI
Iivanainen
Tatu
T
Heikkinen
Sami M
SM
Permi
Perttu
P
Koskela
Harri
H
Kilpeläinen
Ilkka
I
Ylänne
Jari
J
D000199:Actins / Q000737:chemistry*; D000595:Amino Acid Sequence; D002448:Cell Adhesion; D003285:Contractile Proteins / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D003599:Cytoskeleton / Q000378:metabolism; D064448:Filamins; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry*; D008840:Microfilament Proteins / Q000737:chemistry*; D008954:Models, Biological; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry; D012542:Scattering, Radiation
D000199:Actins; D003285:Contractile Proteins; D003432:Cross-Linking Reagents; D064448:Filamins; D007136:Immunoglobulins; D008840:Microfilament Proteins; D011994:Recombinant Proteins