SASDAF8: Human Filamin A Ig-like domains 20-21 truncation (2151-2329)

Basic information

Entry

Database: SASBDB / ID: SASDAF8

Sample

Human Filamin A Ig-like domains 20-21 truncation (2151-2329)

• Human Filamin A Ig-like domains 20-21 (protein), FilaminA, Homo sapiens

Function / homology

Function:

regulation of membrane repolarization during atrial cardiac muscle cell action potential / regulation of membrane repolarization during cardiac muscle cell action potential / establishment of Sertoli cell barrier / Myb complex / glycoprotein Ib-IX-V complex / adenylate cyclase-inhibiting dopamine receptor signaling pathway / formation of radial glial scaffolds / positive regulation of integrin-mediated signaling pathway / : / tubulin deacetylation / actin crosslink formation / blood coagulation, intrinsic pathway / protein localization to bicellular tight junction / OAS antiviral response / positive regulation of actin filament bundle assembly / positive regulation of neuron migration / positive regulation of potassium ion transmembrane transport / Cell-extracellular matrix interactions / early endosome to late endosome transport / Fc-gamma receptor I complex binding / apical dendrite / cell-cell junction organization / positive regulation of neural precursor cell proliferation / positive regulation of platelet activation / protein localization to cell surface / wound healing, spreading of cells / podosome / negative regulation of transcription by RNA polymerase I / megakaryocyte development / GP1b-IX-V activation signalling / positive regulation of axon regeneration / cortical cytoskeleton / receptor clustering / SMAD binding / RHO GTPases activate PAKs / actin filament bundle / brush border / semaphorin-plexin signaling pathway / blood vessel remodeling / cilium assembly / mitotic spindle assembly / epithelial to mesenchymal transition / potassium channel regulator activity / heart morphogenesis / axonal growth cone / release of sequestered calcium ion into cytosol / positive regulation of substrate adhesion-dependent cell spreading / regulation of cell migration / dendritic shaft / protein kinase C binding / protein localization to plasma membrane / actin filament / negative regulation of DNA-binding transcription factor activity / trans-Golgi network / mRNA transcription by RNA polymerase II / G protein-coupled receptor binding / synapse organization / establishment of protein localization / negative regulation of protein catabolic process / cerebral cortex development / small GTPase binding / kinase binding / platelet aggregation / Z disc / positive regulation of protein import into nucleus / actin filament binding / actin cytoskeleton / cell-cell junction / Platelet degranulation / negative regulation of neuron projection development / GTPase binding / actin cytoskeleton organization / angiogenesis / DNA-binding transcription factor binding / positive regulation of canonical NF-kappaB signal transduction / perikaryon / transmembrane transporter binding / postsynapse / protein stabilization / cadherin binding / focal adhesion / negative regulation of apoptotic process / nucleolus / perinuclear region of cytoplasm / glutamatergic synapse / protein homodimerization activity / RNA binding / extracellular exosome / extracellular region / nucleus / membrane / plasma membrane / cytosol / cytoplasm

Domain/homology:

Filamin family / Filamin/ABP280 repeat / Filamin-type immunoglobulin domains / Filamin/ABP280 repeat / Filamin/ABP280 repeat profile. / Filamin/ABP280 repeat-like / Actinin-type actin-binding domain signature 1. / Actinin-type actin-binding domain signature 2. / Actinin-type actin-binding domain, conserved site / Calponin homology domain / Calponin homology (CH) domain / Calponin homology domain / CH domain superfamily / Calponin homology (CH) domain profile. / Immunoglobulin E-set / Immunoglobulin-like fold

Component:

Filamin-A

• Biological species: Homo sapiens (human)
• Citation: Journal: PLoS One / Year: 2015; Title: Flexible Structure of Peptide-Bound Filamin A Mechanosensor Domain Pair 20-21.; Authors: Jonne Seppälä / Helena Tossavainen / Nebojsa Rodic / Perttu Permi / Ulla Pentikäinen / Jari 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 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.

Contact author

• Jonne Seppälä (University of Jyväskylä, Jyväskylän, Finland)

Models

Sample

• Sample: Name: Human Filamin A Ig-like domains 20-21 truncation (2151-2329); Specimen concentration: 1.00-4.00
• Buffer: Name: Tris / Concentration: 20.00 mM / pH: 8 / Composition: 50 mM NaCl, 10mM DTT

Entity #188

Name: FilaminA / Type: protein / Description: Human Filamin A Ig-like domains 20-21 / Formula weight: 18.7 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: P21333
Sequence:

SVANVGSHCD LSLKIPEISI QDMTAQVTSP SGKTHEAEIV EGENHTYCIR FVPAEMGTHT VSVKYKGQHV PGSPFQFTVG PLGEGGAHKV RAGGPGLERA EAGVPAEFSI WTREAGAGGL AIAVEGPSKA EISFEDRKDG SCGVAYVVQE PGDYEVSVKF NEEHIPDSPF VVPVASPS

Experimental information

• Beam: Instrument name: ESRF BM29 / City: Grenoble / 国: France / Type of source: X-ray synchrotron / Wavelength: 0.93 Å / Dist. spec. to detc.: 2.43 mm
• Detector: Name: Pilatus 1M

Scan

Title: Human Filamin A Ig-like domains 20-21 / Measurement date: Feb 1, 2014 / Storage temperature: 20 °C / Exposure time: 1 sec. / Number of frames: 10 / Unit: 1/nm /

	Min	Max
Q	0.0649	4.61

Distance distribution function P(R)

Sofotware P(R): GNOM 4.6 / Number of points: 260 /

	Min	Max
Q	0.1775	2.66
P(R) point	24	283
R	0	8.5

Result

Type of curve: merged
Comments: Filamin A fragment residues 2151-2329 (Ig-like domains). NOTE: The displayed SAXS data and data used for P(r) vs r determination are on different I(s) scales.

	Experimental	Porod	Estimated method
MW	30 kDa	17 kDa	-
Volume	-	28.9 nm3	Datporod

	P(R)	P(R) error	Guinier
Forward scattering, I0	29.9	0.044	27
Radius of gyration, Rg	2.45 nm	0.006	2.43 nm

	Min	Max
D	-	8.5
Guinier point	22	76