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-Structure paper
Title | Flexible Structure of Peptide-Bound Filamin A Mechanosensor Domain Pair 20-21. |
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Journal, issue, pages | PLoS One, Vol. 10, Issue 8, Page e0136969, Year 2015 |
Publish date | Aug 31, 2015 |
![]() | Jonne Seppälä / Helena Tossavainen / Nebojsa Rodic / Perttu Permi / Ulla Pentikäinen / Jari Ylänne / ![]() |
PubMed Abstract | Filamins (FLNs) are large, multidomain actin cross-linking proteins with diverse functions. Besides regulating the actin cytoskeleton, they serve as important links between the extracellular matrix ...Filamins (FLNs) are large, multidomain actin cross-linking proteins with diverse functions. Besides regulating the actin cytoskeleton, they serve as important links between the extracellular matrix and the cytoskeleton by binding cell surface receptors, functioning as scaffolds for signaling proteins, and binding several other cytoskeletal proteins that regulate cell adhesion dynamics. Structurally, FLNs are formed of an amino terminal actin-binding domain followed by 24 immunoglobulin-like domains (IgFLNs). Recent studies have demonstrated that myosin-mediated contractile forces can reveal hidden protein binding sites in the domain pairs IgFLNa18-19 and 20-21, enabling FLNs to transduce mechanical signals in cells. The atomic structures of these mechanosensor domain pairs in the resting state are known, as well as the structures of individual IgFLN21 with ligand peptides. However, little experimental data is available on how interacting protein binding deforms the domain pair structures. Here, using small-angle x-ray scattering-based modelling, x-ray crystallography, and NMR, we show that the adaptor protein migfilin-derived peptide-bound structure of IgFLNa20-21 is flexible and adopts distinctive conformations depending on the presence or absence of the interacting peptide. The conformational changes reported here may be common for all peptides and may play a role in the mechanosensor function of the site. |
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Methods | SAS (X-ray synchrotron) |
Structure data | ![]() SASDAE8: Human Filamin A Ig-like domains 20-21 truncation (2151-2329) in complex with migfilin peptide ![]() SASDAF8: Human Filamin A Ig-like domains 20-21 truncation (2151-2329) ![]() SASDAG8: Human Filamin A Ig-like domains 20-21* truncation (2141-2329) in complex with migfilin peptide ![]() SASDAH8: |
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