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

PloS One
Jonne SeppäläJari Ylänne

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 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 th...Continue Reading

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Citations

Mar 30, 2017·The Journal of Biological Chemistry·Sujay S IthychandaJun Qin
Jul 22, 2017·PLoS Genetics·Nicanor González-MoralesFrieder Schöck
Nov 10, 2017·Journal of Muscle Research and Cell Motility·Mehroz EhsanKatja Gehmlich
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Jul 27, 2017·Annals of Biomedical Engineering·Yajing ShenGustavo R Plaza
Apr 4, 2021·International Journal of Molecular Sciences·Kirsty WadmoreKatja Gehmlich
Apr 17, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jonas K GreitenNicole Endlich

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Methods Mentioned

BETA
x-ray scattering
size-exclusion chromatography
gel filtration
NMR
force spectroscopy measurements
FRET

Software Mentioned

DAMAVER
DATPOROD
SUPCOMB
AUTORG
Sparky
TLSMD
ATSAS
wARP
SASBDB
GAJOE

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