SASDAG8: Human Filamin A Ig-like domains 20-21* truncation (2141-2329) in ...

Basic information

Entry

Database: SASBDB / ID: SASDAG8

Sample

Human Filamin A Ig-like domains 20-21* truncation (2141-2329) in complex with migfilin peptide

• Human Filamin A Ig-like domains 20-21*/migfilin peptide complex (protein), FilaminA*/migfilin, 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 / formation of radial glial scaffolds / Myb complex / adenylate cyclase-inhibiting dopamine receptor signaling pathway / protein localization to bicellular tight junction / positive regulation of integrin-mediated signaling pathway / positive regulation of neuron migration / blood coagulation, intrinsic pathway / OAS antiviral response / actin crosslink formation / positive regulation of actin filament bundle assembly / tubulin deacetylation / megakaryocyte development / Cell-extracellular matrix interactions / positive regulation of platelet activation / positive regulation of potassium ion transmembrane transport / protein localization to cell surface / apical dendrite / Fc-gamma receptor I complex binding / positive regulation of neural precursor cell proliferation / podosome / negative regulation of transcription by RNA polymerase I / wound healing, spreading of cells / GP1b-IX-V activation signalling / receptor clustering / SMAD binding / cortical cytoskeleton / RHO GTPases activate PAKs / semaphorin-plexin signaling pathway / mitotic spindle assembly / potassium channel regulator activity / positive regulation of substrate adhesion-dependent cell spreading / cilium assembly / release of sequestered calcium ion into cytosol / regulation of cell migration / protein localization to plasma membrane / dendritic shaft / actin filament / establishment of protein localization / negative regulation of protein catabolic process / positive regulation of protein import into nucleus / protein sequestering activity / cerebral cortex development / platelet aggregation / mRNA transcription by RNA polymerase II / G protein-coupled receptor binding / small GTPase binding / kinase binding / Z disc / cell-cell junction / actin filament binding / actin cytoskeleton organization / actin cytoskeleton / Platelet degranulation / growth cone / GTPase binding / DNA-binding transcription factor binding / perikaryon / transmembrane transporter binding / positive regulation of canonical NF-kappaB signal transduction / 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 / membrane / nucleus / 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 (2141-2329) in complex with migfilin peptide; Specimen concentration: 1.00-4.00
• Buffer: Name: Tris / Concentration: 20.00 mM / pH: 8 / Composition: 50 mM NaCl, 10mM DTT

Entity #189

Name: FilaminA*/migfilin / Type: protein
Description: Human Filamin A Ig-like domains 20-21*/migfilin peptide complex
Formula weight: 22.6 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: P21333
Sequence:

KESITRRRRA PSVANVGSHC DLSLKIPEIS IQDMTAQVTS PSGKTHEAEI VEGENHTYCI RFVPAEMGTH TVSVKYKGQH VPGSPFQFTV GPLGEGGAHK VRAGGPGLER AEAGVPAEFS IWTREAGAGG LAIAVEGPSK AEISFEDRKD GSCGVAYVVQ EPGDYEVSVK FNEEHIPDSP FVVPVASPS

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 domains 20-21*/migfilin peptide / Measurement date: Feb 1, 2014 / Storage temperature: 20 °C / Exposure time: 1 sec. / Number of frames: 10 / Unit: 1/nm /

	Min	Max
Q	0.0889	4.65

Distance distribution function P(R)

Sofotware P(R): GNOM 4.6 / Number of points: 468 /

	Min	Max
Q	0.243	2.49
P(R) point	33	500
R	0	8.19

Result

Type of curve: merged
Comments: Filamin A fragment residues 2141-2329 (Ig-like domains) in complex with migfilin peptide. NOTE: The displayed SAXS data and data used for P(r) vs r determination are on different relative I(s) scales.

	Experimental	Porod
MW	30 kDa	19.4 kDa
Volume	-	32.9 nm3

	P(R)	Guinier	P(R) error
Forward scattering, I0	30.1	35.8	-
Radius of gyration, Rg	2.41 nm	2.35 nm	0.004

	Min	Max
D	-	8.2
Guinier point	31	83