Flexible Structure of Peptide-Bound Filamin A Mechanosensor Domain Pair 20-21.

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 protein...

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Main Authors: Jonne Seppälä, Helena Tossavainen, Nebojsa Rodic, Perttu Permi, Ulla Pentikäinen, Jari Ylänne
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4554727?pdf=render
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spelling doaj-2ddd870e423d46c58f5c462f62d3f8852020-11-24T20:47:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01108e013696910.1371/journal.pone.0136969Flexible Structure of Peptide-Bound Filamin A Mechanosensor Domain Pair 20-21.Jonne SeppäläHelena TossavainenNebojsa RodicPerttu PermiUlla PentikäinenJari YlänneFilamins (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.http://europepmc.org/articles/PMC4554727?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Jonne Seppälä
Helena Tossavainen
Nebojsa Rodic
Perttu Permi
Ulla Pentikäinen
Jari Ylänne
spellingShingle Jonne Seppälä
Helena Tossavainen
Nebojsa Rodic
Perttu Permi
Ulla Pentikäinen
Jari Ylänne
Flexible Structure of Peptide-Bound Filamin A Mechanosensor Domain Pair 20-21.
PLoS ONE
author_facet Jonne Seppälä
Helena Tossavainen
Nebojsa Rodic
Perttu Permi
Ulla Pentikäinen
Jari Ylänne
author_sort Jonne Seppälä
title Flexible Structure of Peptide-Bound Filamin A Mechanosensor Domain Pair 20-21.
title_short Flexible Structure of Peptide-Bound Filamin A Mechanosensor Domain Pair 20-21.
title_full Flexible Structure of Peptide-Bound Filamin A Mechanosensor Domain Pair 20-21.
title_fullStr Flexible Structure of Peptide-Bound Filamin A Mechanosensor Domain Pair 20-21.
title_full_unstemmed Flexible Structure of Peptide-Bound Filamin A Mechanosensor Domain Pair 20-21.
title_sort flexible structure of peptide-bound filamin a mechanosensor domain pair 20-21.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2015-01-01
description 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.
url http://europepmc.org/articles/PMC4554727?pdf=render
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