6533b82efe1ef96bd1293460
RESEARCH PRODUCT
The C-terminal rod 2 fragment of filamin A forms a compact structure that can be extended
Iain D. CampbellSalla RuskamoGregor HofmannRobert J.c. GilbertUlla PentikäinenJari YlännePengju Jiangsubject
Models Moleculargenetics [Receptors Dopamine D3]metabolism [Recombinant Proteins]Protein Conformationgenetics [Antigens CD18]chemistry [Recombinant Proteins]Plasma protein bindingCrystallography X-RayLigandsFilaminmetabolism [Antigens CD18]metabolism [Cytoskeletal Proteins]BiochemistryfilaminsContractile ProteinsProtein structuremetabolism [Peptide Fragments]FLNAchemistry [Antigens CD18]genetics [Cell Adhesion Molecules]Small-angle X-ray scatteringMicrofilament Proteinsgenetics [Contractile Proteins]Recombinant Proteinschemistry [Receptors Dopamine D3]FBLIM1 protein humanddc:540Domain (ring theory)DimerizationProtein Bindingchemistry [Contractile Proteins]FilaminsAntigens CD18metabolism [Cell Adhesion Molecules]BiologyScattering Small Anglemetabolism [Receptors Dopamine D3]Humanschemistry [Microfilament Proteins]Protein Interaction Domains and Motifsmetabolism [Mutant Proteins]DRD3 protein humanMolecular Biologymetabolism [Contractile Proteins]Actingenetics [Cytoskeletal Proteins]Cryoelectron MicroscopyMutagenesista1182Receptors Dopamine D3metabolism [Microfilament Proteins]Cell Biologychemistry [Cell Adhesion Molecules]genetics [Peptide Fragments]Peptide FragmentsCytoskeletal ProteinsCrystallographychemistry [Mutant Proteins]chemistry [Peptide Fragments]CD18 AntigensBiophysicschemistry [Cytoskeletal Proteins]Mutant Proteinsgenetics [Microfilament Proteins]Cell Adhesion Moleculesdescription
Filamins are large proteins that cross-link actin filaments and connect to other cellular components. The C-terminal rod 2 region of FLNa (filamin A) mediates dimerization and interacts with several transmembrane receptors and intracellular signalling adaptors. SAXS (small-angle X-ray scattering) experiments were used to make a model of a six immunoglobulin-like domain fragment of the FLNa rod 2 (domains 16–21). This fragment had a surprising three-branched structural arrangement, where each branch was made of a tightly packed two-domain pair. Peptides derived from transmembrane receptors and intracellular signalling proteins induced a more open structure of the six domain fragment. Mutagenesis studies suggested that these changes are caused by peptides binding to the CD faces on domains 19 and 21 which displace the preceding domain A-strands (18 and 20 respectively), thus opening the individual domain pairs. A single particle cryo-EM map of a nine domain rod 2 fragment (domains 16–24), showed a relatively compact dimeric particle and confirmed the three-branched arrangement as well as the peptide-induced conformation changes. These findings reveal features of filamin structure that are important for its interactions and mechanical properties.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-08-14 | Biochemical Journal |