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The C-terminal rod 2 fragment of filamin A forms a compact structure that can be extended
Abstract
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- info:eu-repo/semantics/article
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- Antigens, CD18: chemistry
- Antigens, CD18: genetics
- Antigens, CD18: metabolism
- Cell Adhesion Molecules: chemistry
- Cell Adhesion Molecules: genetics
- Cell Adhesion Molecules: metabolism
- Contractile Proteins: chemistry
- Contractile Proteins: genetics
- Contractile Proteins: metabolism
- Cryoelectron Microscopy
- Crystallography, X-Ray
- Cytoskeletal Proteins: chemistry
- Cytoskeletal Proteins: genetics
- Cytoskeletal Proteins: metabolism
- Dimerization
- Humans
- Ligands
- Microfilament Proteins: chemistry
- Microfilament Proteins: genetics
- Microfilament Proteins: metabolism
- Models, Molecular
- Mutant Proteins: chemistry
- Mutant Proteins: metabolism
- Peptide Fragments: chemistry
- Peptide Fragments: genetics
- Peptide Fragments: metabolism
- Protein Binding
- Protein Conformation
- Protein Interaction Domains and Motifs
- Receptors, Dopamine D3: chemistry
- Receptors, Dopamine D3: genetics
- Receptors, Dopamine D3: metabolism
- Recombinant Proteins: chemistry
- Recombinant Proteins: metabolism
- Scattering, Small Angle
- Antigens, CD18
- Cell Adhesion Molecules
- Contractile Proteins
- Cytoskeletal Proteins
- DRD3 protein, human
- FBLIM1 protein, human
- Ligands
- Microfilament Proteins
- Mutant Proteins
- Peptide Fragments
- Receptors, Dopamine D3
- Recombinant Proteins
- filamins